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Wang J, Zhao M, Fu D, Wang M, Han C, Lv Z, Wang L, Liu J. Human neural stem cell-derived extracellular vesicles protect against ischemic stroke by activating the PI3K/AKT/mTOR pathway. Neural Regen Res 2025; 20:3245-3258. [PMID: 39248158 PMCID: PMC11881723 DOI: 10.4103/nrr.nrr-d-23-01144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 05/11/2024] [Accepted: 08/22/2024] [Indexed: 09/10/2024] Open
Abstract
JOURNAL/nrgr/04.03/01300535-202511000-00028/figure1/v/2024-12-20T164640Z/r/image-tiff Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells, and can thus be used as substitutes for stem cells in stem cell therapy, thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived treatments. This lays a foundation for the development of potentially potent new treatment modalities for ischemic stroke. However, the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear, presenting challenges for clinical translation. To promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside, we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic stroke. We found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal apoptosis. The human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase, mammalian target of rapamycin, and protein kinase B, and these effects were reversed by treatment with a phosphoinositide 3-kinase inhibitor. These findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway. Finally, we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety profile. Therefore, human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.
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Affiliation(s)
- Jiayi Wang
- Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China
- Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, Liaoning Province, China
| | - Mengke Zhao
- Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China
- Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, Liaoning Province, China
| | - Dong Fu
- Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, Liaoning Province, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning Province, China
| | - Meina Wang
- Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China
- Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, Liaoning Province, China
| | - Chao Han
- Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China
- Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, Liaoning Province, China
| | - Zhongyue Lv
- Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China
- Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, Liaoning Province, China
| | - Liang Wang
- Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China
- Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, Liaoning Province, China
| | - Jing Liu
- Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China
- Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, Liaoning Province, China
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Wang J, Luo Y, Wu Y, Du F, Shi S, Duan Y, Chen A, Zhang J, Yu S. Single-cell Raman spectroscopy as a novel platform for unveiling the heterogeneity of mesenchymal stem cells. Talanta 2025; 292:127933. [PMID: 40081243 DOI: 10.1016/j.talanta.2025.127933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Revised: 03/06/2025] [Accepted: 03/11/2025] [Indexed: 03/15/2025]
Abstract
Despite the significant potential of mesenchymal stem cells (MSC) therapy in clinical settings, challenges persist regarding the efficient detection of consistency and uniformity of MSC populations. Raman spectroscopy is a fast, convenient, and nondestructive technique to acquire molecular properties of biomolecules across laboratory and mass-production settings. Here we utilized Raman spectroscopy to evaluate the heterogeneity of primary MSC from varying donors, passages, and distinct culture conditions, and compared its effectiveness with conventional techniques such as flow cytometry. Although these MSC exhibited insignificant differences in morphology and surface markers in flow cytometry analysis, they could be distinctly clustered into different populations by Raman spectroscopy and the subsequent machine learning using linear discriminant analysis. Principal component analysis demonstrated limited efficiency in clustering Raman data from diverse sources, which could be enhanced through combination with support vector machine or deterministic finite automation. These findings highlight the sensitivity of Raman spectroscopy in detecting subtle differences. Moreover, the analysis of characteristic Raman peaks attributed to cellular biomolecules in MSC from passages 2 (P2) to P10 revealed a gradual decrease in the levels of nucleic acids, lipids, and proteins with increasing passages, and a significant increase in carotenoids from P8. These results suggest the potential use of Raman spectroscopy to assess cellular biochemical characteristics such as aging, with carotenoids emerging as a potential marker of cell aging. In conclusion, Raman spectroscopy demonstrates the ability to rapidly and non-invasively detect cellular heterogeneity and biochemical status, offering significant potential for quality control in stem cell therapy.
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Affiliation(s)
- Jingwen Wang
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu, 215163, China
| | - Yanjun Luo
- Shanghai D-Band Medical Technology Co., LTD, Shanghai, 201802, China
| | - Yue Wu
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu, 215163, China
| | - Fangzhou Du
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu, 215163, China
| | - Shuaiguang Shi
- School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Yuhan Duan
- School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Aoying Chen
- School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Jingzhong Zhang
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu, 215163, China; Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China; School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230026, China.
| | - Shuang Yu
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu, 215163, China; Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China; School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230026, China.
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3
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Eisa NM, Elshaer SS, Bakry S, Abdelzaher OF, Eldesoky NAR. Placental extract augments mesenchymal stem cells in pancreatic tissue regeneration: A new insight into diabetes treatment. Tissue Cell 2025; 95:102883. [PMID: 40157219 DOI: 10.1016/j.tice.2025.102883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2025] [Revised: 03/19/2025] [Accepted: 03/19/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND Although a wide variety of medicinal interventions and lifestyles have been endeavored so far for the treatment of diabetes mellitus, it is still intractable. The current study aimed to examine the effect of mesenchymal stem cells (MSCs) and/or placental extract (PE) on streptozotocin (STZ) induced diabetic rats. METHODS Fifty male albino rats were used. Ten of them as negative control (group I) and the remaining forty rats were subjected to diabetes induction using 50 mg/kg STZ then divided into; group II (positive controls), group III (MSCs treated), group IV (PE treated), and group V (MSCs/PE combination treated). After 4 weeks of treatment, animals were sacrificed; blood samples were collected for determination of glycated hemoglobin by HPLC, and serum was separated for determination of glucose spectrophotometrically and insulin by ELISA. Pancreatic tissues were harvested for histopathological examination and pancreatic duodenal homeobox 1 (Pdx1) gene expression by PCR. RESULTS The three treated groups showed significant enhancement in glycemic parameters and Pdx1 gene expression compared with positive control group (P < 0.05). Histopathological examination revealed great improvement in the three treated groups where group V showed the best picture and the best glycemic control. CONCLUSIONS This study points to the possible role of PE in DM treatment. The MSCs/PE combination had the ability to return all parameters and Pdx1 gene expression to their normal levels. This action could be attributed to MSCs homing into the pancreas and the pancreatic rejuvenation provided by PE contents of growth factors; EGF, HGF, IGF-1 and IGF-II.
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Affiliation(s)
- Nehal Mohamed Eisa
- Clinical Research Department at Giza health affairs Directorate, MOHP, Giza, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr city, Cairo 11823, Egypt.
| | - Shereen Saeid Elshaer
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr city, Cairo 11823, Egypt
| | - Sayed Bakry
- Zoology Department, Faculty of Science, Al-Azhar University, Cairo, Egypt
| | | | - Noha Abdel-Rahman Eldesoky
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr city, Cairo 11823, Egypt
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Sonawane R, Patil S, Rahaman J, Mukherjee D. Effect of microgravity on bone Tissue: Mechanisms of osteodegeneration and advanced treatment modalities. Biochem Biophys Res Commun 2025; 771:152055. [PMID: 40409112 DOI: 10.1016/j.bbrc.2025.152055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2025] [Revised: 05/17/2025] [Accepted: 05/19/2025] [Indexed: 05/25/2025]
Abstract
Preeminent human existence in space raises concerns about bone health due to the effect of microgravity on bone tissue degeneration. Space experiments pose logistical challenges, but ground-based research using microgravity simulation provides information about bone loss mechanisms. This review compiles and evaluates data from astronaut, animal, and cellular experiments, emphasizing microgravity-induced skeletal deconditioning. These findings contribute to creating treatment approaches for preventing bone loss risks in space and potentially on Earth. Astronauts experience notable bone loss, up to 1 %-2 % per month in a gravity-less environment, predominantly influencing weight-bearing bones. These necessitate finding efficient treatment approaches for preventing bone loss risks in space and potentially on Earth. There is a significant need to investigate microgravity's impact on various bone compartments and skeletal recovery processes. The current review explores the stages of bone remodeling and the fundamental causes of bone loss in microgravity, including effects on osteoblasts, osteocytes, osteoclasts, hematopoietic stem cells, and bone marrow stromal cells, as well as the impact on calcium levels. The article also explores various treatment options, including general management, recent therapies, supportive therapies, and emerging therapies such as BP-NELL-PEG, melatonin, calcitonin, and molecular therapies, highlighting their therapeutic potential against microgravity-induced bone loss.
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Affiliation(s)
- Rushikesh Sonawane
- Department of Pharmaceutics, School of Pharmacy & Technology Management, SVKM's Narsee Monjee Institute of Management Studies, Shirpur, 425405, Maharashtra, India
| | - Saurav Patil
- Department of Pharmaceutics, School of Pharmacy & Technology Management, SVKM's Narsee Monjee Institute of Management Studies, Shirpur, 425405, Maharashtra, India
| | - Jiyaur Rahaman
- Department of Pharmaceutics, School of Pharmacy & Technology Management, SVKM's Narsee Monjee Institute of Management Studies, Shirpur, 425405, Maharashtra, India; Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's Narsee Monjee Institute of Management Studies (NMIMS) Deemed-to-be University, V.L. Mehta road, Vile Parle (West), Mumbai, 400056, Maharashtra, India
| | - Dhrubojyoti Mukherjee
- Department of Pharmaceutics, School of Pharmacy & Technology Management, SVKM's Narsee Monjee Institute of Management Studies, Shirpur, 425405, Maharashtra, India.
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Poudineh M, Mohammadyari F, Parsamanesh N, Jamialahmadi T, Kesharwani P, Sahebkar A. Cell and gene therapeutic approaches in non-alcoholic fatty liver disease. Gene 2025; 956:149466. [PMID: 40189164 DOI: 10.1016/j.gene.2025.149466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Revised: 03/14/2025] [Accepted: 03/31/2025] [Indexed: 04/11/2025]
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) refers to a range of conditions marked by the buildup of triglycerides in liver cells, accompanied by inflammation, which contributes to liver damage, clinical symptoms, and histopathological alterations. Multiple molecular pathways contribute to NAFLD pathogenesis, including immune dysregulation, endoplasmic reticulum stress, and tissue injury. Both the innate and adaptive immune systems play crucial roles in disease progression, with intricate crosstalk between liver and immune cells driving NAFLD development. Among emerging therapeutic strategies, cell and gene-based therapies have shown promise. This study reviews the pathophysiological mechanisms of NAFLD and explores the therapeutic potential of cell-based interventions, highlighting their immunomodulatory effects, inhibition of hepatic stellate cells, promotion of hepatocyte regeneration, and potential for hepatocyte differentiation. Additionally, we examine gene delivery vectors designed to target NAFLD, focusing on their role in engineering hepatocytes through gene addition or editing to enhance therapeutic efficacy.
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Affiliation(s)
| | | | - Negin Parsamanesh
- Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran; Department of Genetics and Molecular Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Tananz Jamialahmadi
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Prashant Kesharwani
- Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar, Madhya Pradesh 470003, India.
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Centre for Research Impact and Outcome, Chitkara University, Rajpura 140417, Punjab, India; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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6
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Amitrano MJ, Cho M, Murphy WL. Screening of Biomaterials for Stem Cell Culture Applications. ACS Biomater Sci Eng 2025. [PMID: 40489652 DOI: 10.1021/acsbiomaterials.5c00088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/11/2025]
Abstract
Stem cells have a considerable role to play in future biomedical breakthroughs due to their therapeutic potential. As stem cells may be studied in a variety of different applications, a "one size fits all" approach to the stem cell culture substrate is not appropriate. Different biomaterial formulations may be necessary in different contexts. Screening can help identify biomaterials for specific applications to harness stem cells' full potential. In this review, we cover experimental setups appropriate for screening applications, as well as data collection tools for both material and cell characterization. Finally, we cover high throughput data processing techniques, emphasizing the potential of introducing machine learning (ML) techniques into the analytical process. With increased use of ML-based analytical techniques, biomaterial screening has the potential to contribute to the rapid development of biomaterials for targeted stem cell applications.
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Affiliation(s)
- Margot J Amitrano
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States
| | - Mina Cho
- Department of Materials Science and Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States
| | - William L Murphy
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States
- Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States
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7
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Lee G, Kim YH, Kim D, Lee DH, Bhang SH, Lee K. PCL-fibrin-alginate hydrogel based cell co-culture system for improving angiogenesis and immune modulation in limb ischemia. Colloids Surf B Biointerfaces 2025; 250:114553. [PMID: 39921993 DOI: 10.1016/j.colsurfb.2025.114553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Revised: 12/10/2024] [Accepted: 02/02/2025] [Indexed: 02/10/2025]
Abstract
Stem cell therapy has demonstrated promise in regenerative medicine due to their ability to differentiate into various cell types and secrete growth factors. However, challenges such as poor survival rate of transplanted cells under ischemic and immune conditions limit its effectiveness. To address these issues, we developed a polycaprolactone (PCL)-fibrin-alginate matrix hydrogel, which combines adipose-derived stem cells and human umbilical vein endothelial cells with a PCL fiber, encapsulated within fibrin and alginate hydrogel to enhance cell survival, proliferation, and immune modulation. This structure offers protection to the encapsulated cells, supports angiogenesis, and modulates the immune response, significantly improving therapeutic outcomes in a mouse model of hindlimb ischemia. Our in vitro and in vivo results demonstrate the scaffold's ability to support cell viability, promote angiogenesis, and modulate inflammatory responses, indicating its potential as a promising platform for ischemic tissue repair and regenerative medicine. This innovative approach to cell-based therapy highlights the importance of scaffold design in enhancing the therapeutic efficacy of stem cell treatments for ischemic diseases.
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Affiliation(s)
- Gyubok Lee
- Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea
| | - Yeong Hwan Kim
- School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Dongwoo Kim
- Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea
| | - Dong-Hyun Lee
- School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Suk Ho Bhang
- School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
| | - Kangwon Lee
- Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea.
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8
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Lin P, Lin Y, Lu Y, Chen X, Zhou Z, Zhao X, Cui L. Unveiling the dynamic drivers: phase separation's pivotal role in stem cell biology and therapeutic potential. Stem Cell Res Ther 2025; 16:266. [PMID: 40442783 PMCID: PMC12123740 DOI: 10.1186/s13287-025-04403-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Accepted: 05/16/2025] [Indexed: 06/02/2025] Open
Abstract
Phase separation is fundamental for cellular organization and function, profoundly impacting a range of biological processes from gene expression to cellular signaling pathways, pivotal in stem cell biology. This review explores the primary types of phase separation and their mechanisms, emphasizing how phase separation is integral to maintaining cellular integrity and its significant implications for disease progression. It elaborates on current insights into how phase separation influences stem cell biology, discussing the challenges in translating these insights into practical applications. These challenges stem from the complex dynamics of phase separation, the need for advanced imaging techniques, and the necessity for real-time, in situ analysis within living systems. Addressing these challenges through innovative methodologies and gaining a deeper understanding of the molecular interactions that govern phase separation in stem cells are essential for developing precise, targeted therapies. Ultimately, advancing our understanding of phase separation could transform stem cell-based therapeutic approaches, opening up novel strategies for disease treatment and advancements in regenerative medicine.
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Affiliation(s)
- Pei Lin
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, Guangdong, China
| | - Yunfan Lin
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, Guangdong, China
| | - Ye Lu
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, Guangdong, China
| | - Xu Chen
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, Guangdong, China
| | - Zihao Zhou
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, Guangdong, China
| | - Xinyuan Zhao
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, Guangdong, China.
| | - Li Cui
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, Guangdong, China.
- School of Dentistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
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Fu Y, Qiu Z, Cao Y, Jiang M, Cui X. Hydrogel-exosome complexes: a novel strategy for cardiovascular regeneration. NANOSCALE 2025. [PMID: 40434070 DOI: 10.1039/d5nr00892a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2025]
Abstract
Cardiovascular disease (CVD) remains one of the leading causes of high mortality and morbidity worldwide, posing a substantial threat to global health. Mesenchymal stem cell (MSC) therapy has emerged as a promising treatment approach, primarily through the secretion of various bioactive factors. Exosomes (Exos), in particular, stand out as the most effective components, as their noncoding RNA and proteins play a crucial role in promoting the repair of cardiac function, positioning them a promising cell-free therapy for CVD. However, challenges such as poor stability, low delivery efficiency, weak targeting, and rapid immune-mediated clearance hinder the broader application of Exos, presenting significant obstacles for further clinical translation. Recent advancements in biomaterials, particularly hydrogels, offer new avenues for Exos-based CVD therapies. Hydrogels, with their ability to improve stability, release control, and targeting, have gained considerable attention in the biomedical field. This review explores the latest research developments regarding the treatment of CVD using Exos, and highlights their synergistic application with hydrogels, which provide valuable insights for advancing Exos-based therapies and developing novel therapeutic strategies for CVD.
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Affiliation(s)
- Yonglin Fu
- School of Basic Medical Sciences, Guangdong Medical University, Dongguan, 523808, China.
| | - Zixiong Qiu
- School of Basic Medical Sciences, Guangdong Medical University, Dongguan, 523808, China.
| | - Yifang Cao
- School of Basic Medical Sciences, Guangdong Medical University, Dongguan, 523808, China.
| | - Mei Jiang
- School of Basic Medical Sciences, Guangdong Medical University, Dongguan, 523808, China.
| | - Xiaojun Cui
- School of Basic Medical Sciences, Guangdong Medical University, Dongguan, 523808, China.
- Kashi University School of Medicine, Xinjiang, 844000, China
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Gao Y, Liu D, Xiao Q, Huang S, Li L, Xie B, Zhou L, Qi Y, Liu Y. Exploration of Pathogenesis and Cutting-Edge Treatment Strategies of Sarcopenia: A Narrative Review. Clin Interv Aging 2025; 20:659-684. [PMID: 40438271 PMCID: PMC12117577 DOI: 10.2147/cia.s517833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 05/12/2025] [Indexed: 06/01/2025] Open
Abstract
Sarcopenia a progressive and multifactorial musculoskeletal syndrome characterized by loss of muscle mass and function, poses a significant global health challenge, particularly in aging populations. Epidemiological studies reveal that sarcopenia affects approximately 5-10% of the general population, with prevalence rates escalating dramatically after age 60 to reach 10-27% in older adults. This age-associated increase contributes significantly to healthcare burdens by elevating risks of disability, frailty, and mortality. Despite its profound impact, current clinical approaches to sarcopenia remain limited. While resistance exercise and protein supplementation form the cornerstone of management, their efficacy is often constrained by poor long-term adherence and variable individual responses, highlighting the urgent need for more comprehensive and personalized treatment strategies. The pathogenesis of sarcopenia is complex and influenced by various factors, including aging, inflammation, nutritional deficits, physical inactivity, and mitochondrial dysfunction. However, the precise molecular mechanisms underlying this condition are still not fully understood. Recent research has made significant strides in elucidating the intricate mechanisms contributing to sarcopenia, revealing novel insights into its molecular and cellular underpinnings. Notably, emerging evidence points to the pivotal role of mitochondrial dysfunction, altered myokine profiles, and neuromuscular junction degeneration in sarcopenia progression. Additionally, breakthroughs in stem cell therapy, exosome-based treatments, and precision nutrition offer promising avenues for clinical intervention. This review aims to synthesize the latest advancements in sarcopenia research, focusing on the novel contributions to its pathogenesis and treatment strategies. We explore emerging trends such as the role of cellular senescence, epigenetic regulation, and targeted therapeutic interventions that could reshape future approaches to managing sarcopenia. By highlighting recent breakthroughs and cutting-edge research, we hope to advance the understanding of sarcopenia and foster the translation of these findings into effective clinical therapies.
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Affiliation(s)
- Yin Gao
- Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Infectious Diseases, Institute of Clinical Medicine, Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang, 524037, People’s Republic of China
- Marine Medical Research Institute of Zhanjiang, School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang, 524023, People’s Republic of China
| | - Di Liu
- Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Infectious Diseases, Institute of Clinical Medicine, Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang, 524037, People’s Republic of China
- Marine Medical Research Institute of Zhanjiang, School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang, 524023, People’s Republic of China
| | - Qixian Xiao
- Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Infectious Diseases, Institute of Clinical Medicine, Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang, 524037, People’s Republic of China
| | - Shan Huang
- Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Infectious Diseases, Institute of Clinical Medicine, Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang, 524037, People’s Republic of China
- Marine Medical Research Institute of Zhanjiang, School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang, 524023, People’s Republic of China
| | - Li Li
- Marine Medical Research Institute of Zhanjiang, School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang, 524023, People’s Republic of China
| | - Baocheng Xie
- Department of Pharmacy, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital), Dongguan, 52305, People’s Republic of China
| | - Limin Zhou
- Department of Pharmacy, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital), Dongguan, 52305, People’s Republic of China
| | - Yi Qi
- Marine Medical Research Institute of Zhanjiang, School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang, 524023, People’s Republic of China
| | - Yanzhi Liu
- Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Infectious Diseases, Institute of Clinical Medicine, Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang, 524037, People’s Republic of China
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Morakhia KR, Shah AC, Patel MP, Shah JK, Patel R, Chorawala MR. From current landscape to future horizon in stem cell therapy for tissue regeneration and wound healing: bridging the gap. Z NATURFORSCH C 2025:znc-2025-0020. [PMID: 40420770 DOI: 10.1515/znc-2025-0020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Accepted: 04/27/2025] [Indexed: 05/28/2025]
Abstract
Stem cell therapy has emerged as a groundbreaking approach in regenerative medicine, offering immense potential for tissue regeneration and wound healing. Stem cells, with their ability to self-renew and differentiate into specialized cell types, provide innovative therapeutic strategies for variety of medical conditions. Key stem cell types, including embryonic, induced pluripotent, and adult stem cells such as mesenchymal and hematopoietic stem cells, play pivotal roles in regenerative processes and wound repair. In tissue regeneration, stem cells replenish damaged or necrotic cells by differentiating into specialized cell types like bone, muscle, or nerve cells, thus restoring the structural and functional integrity of tissues. In wound healing, stem cells stimulate angiogenesis, generate new skin cells, and modulate immune responses to enhance repair. This multifaceted therapeutic potential has paved the way for clinical applications in cardiovascular, neurological, musculoskeletal, and autoimmune disorders, as well as skin and burn injuries. This review highlights recent advancements in stem cell therapy, exploring its clinical applications and addressing challenges such as immune rejection, ethical concerns, scalability, and the need for long-term clinical trials. The article underscores the importance of continued research to fully realize the transformative potential of stem cell therapy in modern medicine.
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Affiliation(s)
- Kashvy R Morakhia
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Ahmedabad 380009, Gujarat, India
| | - Aayushi C Shah
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Ahmedabad 380009, Gujarat, India
| | - Mannat P Patel
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Ahmedabad 380009, Gujarat, India
| | - Jainam K Shah
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Ahmedabad 380009, Gujarat, India
| | - Rajanikant Patel
- Department of Product Development, Granules Pharmaceuticals Inc., 3701 Concorde Parkway, Chantilly, VA 20151, USA
| | - Mehul R Chorawala
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Ahmedabad 380009, Gujarat, India
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Shi X, Zhang L, Lou J, Zhang K, He Y, Wang W, Liu H, Zhang T, Li C. Injectable hydrogels based on biological macromolecules and intervertebral disc-derived stem cells for intervertebral disc degeneration repair: A review. Int J Biol Macromol 2025; 315:144476. [PMID: 40412681 DOI: 10.1016/j.ijbiomac.2025.144476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2025] [Revised: 05/04/2025] [Accepted: 05/19/2025] [Indexed: 05/27/2025]
Abstract
Intervertebral disc degeneration (IDD) is the fundamental pathological process underlying spinal degenerative diseases. Recent studies on early intervention strategies for delaying and repairing IDD have become a pivotal focus in spinal surgery. Injectable hydrogels synthesized from biological macromolecules, such as polyvinyl alcohol, polyethylene glycol, gelatin, and chitosan, and stem cells have garnered significant attention due to their potential for biomimetic intervertebral disc repair, particularly intervertebral disc-derived stem cells (IVD-SCs). Notably, IVD-SCs exhibit unique tissue-specific characteristics. A comprehensive literature review revealed a limited number of studies investigating the combined application of injectable hydrogels and IVD-SCs for IDD repair. Therefore, we present a comprehensive overview of the development and application of injectable hydrogels and IVD-SCs in IDD repair, detailing their isolation, characterization, clinical translation, associated challenges, and future perspectives. We provide novel insights and directions for advancing future IDD regenerative therapies.
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Affiliation(s)
- Xuewen Shi
- Department of Orthopedics, The First School of Clinical Medicine, Lanzhou University, Lanzhou 730030, China; Department of Orthopedics, The First Hospital of Lanzhou University, Lanzhou 730030, China; The Key Lab of Stem Cells and Gene Drugs of Gansu Province, Lanzhou 730050, China
| | - Lixia Zhang
- Pediatric Respiratory Department, Gansu Provincial Maternal and Child Health Hospital, Lanzhou 730050, China; Pediatric Respiratory Department, Gansu Provincial Central Hospital, Lanzhou 730050, China
| | - Jinpeng Lou
- Department of Orthopedics, The First School of Clinical Medicine, Lanzhou University, Lanzhou 730030, China; Department of Orthopedics, The First Hospital of Lanzhou University, Lanzhou 730030, China
| | - Kui Zhang
- Department of Orthopedics, The First School of Clinical Medicine, Lanzhou University, Lanzhou 730030, China; Department of Orthopedics, The First Hospital of Lanzhou University, Lanzhou 730030, China
| | - Yixiang He
- Department of Orthopedics, The First School of Clinical Medicine, Lanzhou University, Lanzhou 730030, China; Department of Orthopedics, The First Hospital of Lanzhou University, Lanzhou 730030, China
| | - Wenji Wang
- Department of Orthopedics, The First School of Clinical Medicine, Lanzhou University, Lanzhou 730030, China; Department of Orthopedics, The First Hospital of Lanzhou University, Lanzhou 730030, China.
| | - Hua Liu
- Orthopedic Center, The 940(th) Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, China.
| | - Tao Zhang
- Orthopedic Center, The 940(th) Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, China.
| | - Chuangbing Li
- Orthopedic Center, The 940(th) Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, China.
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Francius G, Audoux K, Gaye I, Guedon E, Chebil L. Impact of Substrate Surface Chemistry on Wharton's Jelly Mesenchymal Stem Cell Morphological Characteristics, Adherence, and Detachment. ACS APPLIED BIO MATERIALS 2025; 8:4033-4045. [PMID: 40278837 DOI: 10.1021/acsabm.5c00160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2025]
Abstract
Using a multidisciplinary approach combining cell biology assays and physicochemical analyses, the effect of surface chemistry, usually involved in 2D and 3D cell cultures, on the adherence and detachment of Wharton's jelly mesenchymal stem cells (WJ-MSC) was clearly characterized. Values calculated from AFM measurements showed that the Young's modulus of the cells depends on the coating substrate: diethylaminoethyl-dextran (DEAE-D) and carboxypolystyrene (cPS). The adhesion of WJ-MSC was influenced by the composition, charge, and Young's modulus of the surface. High adhesion was observed on DEAE-D. Increasing the wall shear stress decreased the proportion of attached cells on DEAE-D down to ∼20%. For the cPS-coated glass substrate, the fraction of detached cells was higher than that for the DEAE-D surfaces, and at the end of the experiment (maximum wall shear stress of 1 Pa), almost complete detachment was achieved. The experimental strategy used in this work provides information in the field of surface chemistry and may help in the selection and design of efficient microcarriers for cell attachment and detachment during bioreactor cultivation.
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Affiliation(s)
| | - Kévin Audoux
- Université de Lorraine, CNRS, LRGP, F-54000 Nancy, France
| | - Ibrahima Gaye
- Université de Lorraine, CNRS, LRGP, F-54000 Nancy, France
| | | | - Latifa Chebil
- Université de Lorraine, CNRS, LRGP, F-54000 Nancy, France
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Kumar D, Gupta S, Gupta V, Tanwar R, Chandel A. Engineering the Future of Regenerative Medicines in Gut Health with Stem Cell-Derived Intestinal Organoids. Stem Cell Rev Rep 2025:10.1007/s12015-025-10893-w. [PMID: 40380985 DOI: 10.1007/s12015-025-10893-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/05/2025] [Indexed: 05/19/2025]
Abstract
The advent of intestinal organoids, three-dimensional structures derived from stem cells, has significantly advanced the field of biology by providing robust in vitro models that closely mimic the architecture and functionality of the human intestine. These organoids, generated from induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), or adult stem cells, possess remarkable capabilities for self-renewal, differentiation into diverse intestinal cell types, and functional recapitulation of physiological processes, including nutrient absorption, epithelial barrier integrity, and host-microbe interactions. The utility of intestinal organoids has been extensively demonstrated in disease modeling, drug screening, and personalized medicine. Notable examples include iPSC-derived organoids, which have been effectively employed to model enteric infections, and ESC-derived organoids, which have provided critical insights into fetal intestinal development. Patient-derived organoids have emerged as powerful tools for investigating personalized therapeutics and regenerative interventions for conditions such as inflammatory bowel disease (IBD), cystic fibrosis, and colorectal cancer. Preclinical studies involving transplantation of human intestinal organoids into murine models have shown promising outcomes, including functional integration, epithelial restoration, and immune system interactions. Despite these advancements, several challenges persist, particularly in achieving reproducibility, scalability, and maturation of organoids, which hinder their widespread clinical translation. Addressing these limitations requires the establishment of standardized protocols for organoid generation, culture, storage, and analysis to ensure reproducibility and comparability of findings across studies. Nevertheless, intestinal organoids hold immense promise for transforming our understanding of gastrointestinal pathophysiology, enhancing drug development pipelines, and advancing personalized medicine. By bridging the gap between preclinical research and clinical applications, these organoids represent a paradigm shift in the exploration of novel therapeutic strategies and the investigation of gut-associated diseases.
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Affiliation(s)
- Dinesh Kumar
- School of Pharmacy, Desh Bhagat University, Mandi Gobindgarh, Punjab, India.
| | - Sonia Gupta
- Swami Devi Dyal Group of Professional Institute, Panchkula, India
| | - Vrinda Gupta
- School of Pharmacy, Desh Bhagat University, Mandi Gobindgarh, Punjab, India
| | - Rajni Tanwar
- School of Pharmacy, Desh Bhagat University, Mandi Gobindgarh, Punjab, India
| | - Anchal Chandel
- School of Pharmacy, Desh Bhagat University, Mandi Gobindgarh, Punjab, India
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15
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Liu Y, Zhou Z, Lu G, Zhang X, Shi D, Tong L, Chen D, Tuan RS, Li ZA. Musculoskeletal organoids: An emerging toolkit for establishing personalized models of musculoskeletal disorders and developing regenerative therapies. Acta Biomater 2025:S1742-7061(25)00362-9. [PMID: 40381929 DOI: 10.1016/j.actbio.2025.05.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2025] [Revised: 05/09/2025] [Accepted: 05/14/2025] [Indexed: 05/20/2025]
Abstract
Musculoskeletal (MSK) conditions are the primary cause of physical disability globally. These disorders are physically and mentally debilitating and severely impact the patients' quality of life. As the median age of the world's population increases, there has been an intensifying urgency of developing efficacious therapies for various orthopaedic conditions. Furthermore, the highly heterogeneous nature of MSK conditions calls for a personalized approach to studying disease mechanisms and developing regenerative treatments. Organoids have emerged as an advanced approach to generating functional tissue/organ mimics in vitro, which hold promise in MSK regeneration, disease modeling, and therapeutic development. Herein, we review the preparation, characterization, and application of various MSK organoids. We highlight the potential of patient-specific organoids in the development of personalized medicine and discuss the challenges and opportunities in the future development of MSK organoids. STATEMENT OF SIGNIFICANCE: Despite decades of research, translation of MSK research into clinical applications remains limited, partially attributed to our inadequate understanding of disease mechanisms. To advance therapeutic development, there are critical needs for MSK disease models with higher clinical relevance and predictive power. Additionally, engineered constructs that closely mimic the structural and functional features of native MSK tissues are highly desirable. MSK organoids have emerged as a promising approach to meet the above requirements. To unleash the full potential of MSK organoids necessitates a comprehensive understanding of their categories, construction, development, functions, applications, and challenges. This review aims to fulfill this crucial need, aiming to accelerate the clinical translation of MSK organoid platforms to benefit millions of patients afflicted with MSK conditions.
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Affiliation(s)
- Yuwei Liu
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, PR China; Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Sports Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, Guangdong, PR China
| | - Zhilong Zhou
- Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Gang Lu
- Institute for Tissue Engineering and Regenerative Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Hong Kong Special Administrative Region of China
| | - Xin Zhang
- Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, 100191 PR China
| | - Dongquan Shi
- Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, PR China
| | - Liping Tong
- Research Center for Computer-aided Drug Discovery, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China
| | - Di Chen
- Research Center for Computer-aided Drug Discovery, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China; Department of Pharmacology, Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen 518000, PR China.
| | - Rocky S Tuan
- Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Institute for Tissue Engineering and Regenerative Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Hong Kong Special Administrative Region of China.
| | - Zhong Alan Li
- Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Institute for Tissue Engineering and Regenerative Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Hong Kong Special Administrative Region of China; Peter Hung Pain Research Institute, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region of China.
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16
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Begh MZA, Zehravi M, Bhuiyan MAK, Molla MR, Raman K, Emran TB, Ullah MH, Ahmad I, Osman H, Khandaker MU. Recent advances in stem cell approaches to neurodegeneration: A comprehensive review with mechanistic insight. Pathol Res Pract 2025; 271:156013. [PMID: 40381433 DOI: 10.1016/j.prp.2025.156013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2025] [Revised: 05/10/2025] [Accepted: 05/12/2025] [Indexed: 05/20/2025]
Abstract
The progressive nature of neurodegenerative diseases (NDs), such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis, presents substantial problems because current treatments are still obscure. Stem cell-based treatments are emerging as a viable solution to address the significant gaps in treating these severe diseases. This study provides a comprehensive analysis of the latest advancements in stem cell research, focusing on the treatment of NDs. Various types of stem cells, such as adult, induced pluripotent, and embryonic stem cells, and their potential applications in immunomodulation, neurotrophic factor release, and neuronal development are also discussed. Recent clinical studies reveal outcomes, challenges, and solutions, with advancements in disease-specific neural cell production, gene editing, and improved stem cell transplantation transport strategies. The review discussed future perspectives on developing more effective stem cell-based interventions. Biomaterials are being used for cell distribution and personalized medicine techniques to improve treatment outcomes, while exploring stem cell treatments for NDs and identifying areas for further research.
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Affiliation(s)
- Md Zamshed Alam Begh
- Department of Pharmacy, Faculty of Health and Life Sciences, Daffodil International University, Dhaka 1216, Bangladesh.
| | - Mehrukh Zehravi
- Department of Clinical Pharmacy, College of Dentistry & Pharmacy, Buraydah Private Colleges, Buraydah 51418, Saudi Arabia.
| | | | - M Raju Molla
- Department of Pharmacy, Atish Dipankar University of Science and Technology, Dhaka 1230, Bangladesh
| | - Kannan Raman
- Department of Pharmacology, St. John's College of Pharmaceutical Sciences & Research, Kattappana, Idukki, Kerala, India
| | - Talha Bin Emran
- Department of Pharmacy, Faculty of Health and Life Sciences, Daffodil International University, Dhaka 1216, Bangladesh
| | - Md Habib Ullah
- Department of Physics, American International University-Bangladesh (AIUB), 408/1, Kuratoli, Khilkhet, Dhaka 1229, Bangladesh
| | - Irfan Ahmad
- Department of Clinical Laboratory Sciences, College of Applied Medical Science, King Khalid University, Abha, Saudi Arabia
| | - Hamid Osman
- Department of Radiological Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi Arabia
| | - Mayeen Uddin Khandaker
- Applied Physics and Radiation Technologies Group, CCDCU, Faculty of Engineering and Technology, Sunway University, Bandar Sunway, 47500 Selangor, Malaysia; Department of Physics, College of Science, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea
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17
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Bhanothu V. Investigation of the morphological, cellular, biochemical, and molecular modifications in the BG01V human embryonic stem cell-derived neuronal cells. Tissue Cell 2025; 96:102965. [PMID: 40373613 DOI: 10.1016/j.tice.2025.102965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 04/30/2025] [Accepted: 05/06/2025] [Indexed: 05/17/2025]
Abstract
Changes in the morphology, metabolic activity, intracellular calcium (Ca2 +) transients, expression of topoisomerase-2β (Topo-2β), and senescence of human embryonic stem cells (hESCs)-derived neuronal cells on basic hESC culture media and neuronal differentiation medium at different time intervals is not clear. Hence, we aimed to investigate the morphological, cellular, biochemical, and molecular alterations in the BG01V hESC-derived neuronal cells on basic hESC culture media and neuronal differentiation media at different time intervals. MATERIALS AND METHODS BG01V hESC-derived neuronal cells grown on basic hESC culture media and neuronal differentiation media were evaluated for morphological changes by microscopy, metabolic activity by MTT assay, cell viability by Trypan Blue exclusion assay, cellular activity by estimating the Ca2+ deposits, cellular senescence by senescence-associated beta-galactosidase (SA-β-gal) activity, and level of Topo-2β using Western blotting at different time intervals. RESULTS Contrasting to the BG01V hESCs grown on basic hESC culture media, a notable increase in the neuronal cell-like structures, neuritic outgrowth, and expression of nestin protein on neural induction was observed. Higher levels of Ca2+ deposits, metabolic activity, SA-β-gal activity, and Topo-2β expression in BG01V hESC-derived neuronal cells grown on neuronal differentiation media on day 12 compared to hESCs grown on basic hESC culture media including other days were noted. CONCLUSION This study suggests the increase of calcium salts reflecting the calcium activity at distinct phases of neuronal differentiation, ranging from neural induction to neurite extension. The metabolic and SA-β-gal activity of BG01V hESC-derived neuronal cells may suggest the ongoing biological aging process. Upregulation and activation of Topo-2β upon differentiation induction at the mid-phase suggest the activation of inducible gene loci and downregulation of Topo-2β at a later stage.
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Affiliation(s)
- Venkanna Bhanothu
- Department of Cell Biology, ICMR-National Institute of Nutrition, Tarnaka, Hyderabad, India; Department of Biotechnology & Bioinformatics, School of life Sciences, University of Hyderabad, Hyderabad, India.
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18
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Wang Y, Wu B, Tao Y, Wang M, Wu D, Chen E, Tang H. Therapeutic effect of hUC-MSCs from different transplantation routes on acute liver failure in rats. Front Med (Lausanne) 2025; 12:1525719. [PMID: 40417693 PMCID: PMC12098624 DOI: 10.3389/fmed.2025.1525719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Accepted: 04/28/2025] [Indexed: 05/27/2025] Open
Abstract
Objective Acute liver failure (ALF) is a rare yet serious clinical syndrome. Recent studies have indicated that stem cells can effectively treat this condition. However, the optimal route for stem cell transplantation in the treatment of ALF remains unclear. This study aims to investigate the most effective transplantation route for stem cell therapy in ALF. Methods Human umbilical cord mesenchymal stem cells (hUC-MSCs) expressing both luciferase and green fluorescent protein were generated using a lentiviral vector. The hUC-MSCs were transplanted via the tail vein, portal vein, and abdominal cavity. The survival and distribution of the transplanted hUC-MSCs in rats were assessed through in vivo imaging and immunofluorescence. Furthermore, the therapeutic effects of hUC-MSCs transplanted via different routes on ALF were compared. Results The survival time of hUC-MSCs transplanted via the tail vein and portal vein was shorter compared to those transplanted intraperitoneally. The distribution of hUC-MSCs varied by transplantation route: those injected via the tail vein and portal vein were primarily found in the lungs and liver, respectively, while intraperitoneally transplanted hUC-MSCs predominantly localized in the abdominal cavity. In ALF rats, hUC-MSCs transplanted via the tail vein and portal vein improved survival rates, enhanced liver pathology, and reduced levels of inflammatory cytokines in liver tissue. In contrast, abdominal transplantation of hUC-MSCs showed no significant therapeutic effect. Conclusion hUC-MSCs transplanted via the tail vein and portal vein exhibited similar therapeutic effects on ALF; however, abdominal transplantation of hUC-MSCs showed no significant effect.
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Affiliation(s)
- Yonghong Wang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
- Laboratory of Infectious and Liver Diseases, Institution of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
| | - Bei Wu
- Department of Hepatology, Public Health Clinical Center of Chengdu, Chengdu, China
| | - Yachao Tao
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
- Laboratory of Infectious and Liver Diseases, Institution of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
| | - Menglan Wang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
- Laboratory of Infectious and Liver Diseases, Institution of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
| | - Dongbo Wu
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
- Laboratory of Infectious and Liver Diseases, Institution of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
| | - Enqiang Chen
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
- Laboratory of Infectious and Liver Diseases, Institution of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
- Laboratory of Infectious and Liver Diseases, Institution of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
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Sarji M, Ankawa R, Yampolsky M, Fuchs Y. A near death experience: The secret stem cell life of caspase-3. Semin Cell Dev Biol 2025; 171:103617. [PMID: 40344690 DOI: 10.1016/j.semcdb.2025.103617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2025] [Revised: 04/03/2025] [Accepted: 04/07/2025] [Indexed: 05/11/2025]
Abstract
Caspase-3 is known to play a pivotal role in mediating apoptosis, a key programmed cell death pathway. While extensive research has focused on understanding how caspase-3 is activated and functions during apoptosis, emerging evidence has revealed its significant non-apoptotic roles across various cell types, including stem cells. This review explores the critical involvement of caspase-3 in regulating stem cell properties, maintaining stem cell populations, and facilitating tissue regeneration. We also explore the potential pathological consequences of caspase-3 dysfunction in stem cells and cancer cells alongside the therapeutic opportunities of targeting caspase-3.
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Affiliation(s)
- Mahasen Sarji
- Faculty of Biology, Technion Israel Institute of Technology, Haifa, 3200003, Israel
| | - Roi Ankawa
- Augmanity, Rehovot, Israel; Elixr Bio, Rehovot, Israel
| | | | - Yaron Fuchs
- Augmanity, Rehovot, Israel; Elixr Bio, Rehovot, Israel.
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20
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Zhang D, Li H. Epidemiology, etiology and treatment of female vaginal injury. Reprod Health 2025; 22:65. [PMID: 40329296 PMCID: PMC12057040 DOI: 10.1186/s12978-025-02017-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Accepted: 04/20/2025] [Indexed: 05/08/2025] Open
Abstract
The preservation of vaginal anatomical structure and physiological function is critical for women's health and should not be ignored. Vaginal injuries have a negative impact on women's quality of life. Vaginal delivery is the most common cause of vaginal injuries, 53-79% of women suffer from perineal and vaginal lacerations during labor. The incident of vaginal atrophy caused by decreased estrogen in menopausal women is growing, reaching 39%. The primary medical treatment of menopause-related vaginal atrophy is estrogen, which has a recognized therapeutic effect. Severe obstetric lacerations and trauma-related vaginal damage must be identified promptly and treated surgically. Radiotherapy-induced vaginal stenosis and adhesion could be treated with a vaginal dilator, however, there is a lack of consensus on therapy plans. Furthermore, surgical closure of genitourinary fistulas arise from the tumor or vaginal delivery is technically challenging. Stem cells have been proven to be effective in treating vaginal atrophy in animal models. Traditional treatments for Mayer-Rokitansky-Küster-Hauser syndrome, which is caused by a congenital anomaly of vaginal development, include vaginal dilation and vaginoplasty with autologous tissue. However, due to poor compliance and surgical complications, tissue engineering technology has received considerable attention for vaginal reconstruction because of its preferred characteristics. Nonetheless, the biological therapy of stem cell and tissue engineering technology still faces severe challenges, without application for clinical translation. Therefore, for women with vaginal injuries, the choice of treatment should be guided by the etiology and symptom severity. Stem cell therapy and tissue engineering technology show promising application prospects for vaginal injury repair and reconstruction, in addition to medical and surgical treatments. However, it is necessary to conduct additional pre-clinical animals and clinical trials in order to provide reliable references for future clinical practice.
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Affiliation(s)
- Di Zhang
- Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Hua Li
- Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
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21
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Goff AD, Zhang X, Thomas B, Ong SSY, Atala A, Zhang Y. Body Fluid-Derived Stem Cells: Powering Innovative, Less-Invasive Cell Therapies. Int J Mol Sci 2025; 26:4382. [PMID: 40362618 PMCID: PMC12072510 DOI: 10.3390/ijms26094382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2025] [Revised: 05/02/2025] [Accepted: 05/02/2025] [Indexed: 05/15/2025] Open
Abstract
Stem cell therapy offers significant promise for tissue regeneration and repair. Traditionally, bone marrow- and adipose-derived stem cells have served as primary sources, but their clinical use is limited by invasiveness and low cell yield. This review focuses on body fluid-derived stem cells as an emerging, non-invasive, and readily accessible alternative. We examine stem cells isolated from amniotic fluid, peripheral blood, cord blood, menstrual fluid, urine, synovial fluid, breast milk, and cerebrospinal fluid, highlighting their unique biological properties and therapeutic potential. By comparing their characteristics and barriers to clinical translation, we propose body fluid-derived stem cells as a promising source for regenerative applications, with continued research needed to fully achieve their clinical utility.
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Affiliation(s)
- Adam David Goff
- Wake Forest Institute for Regenerative Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA; (A.D.G.); (X.Z.)
- School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA
| | - Xinyue Zhang
- Wake Forest Institute for Regenerative Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA; (A.D.G.); (X.Z.)
| | - Biju Thomas
- Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90033, USA
| | - Sally Shin Yee Ong
- Department of Ophthalmology, School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA
| | - Anthony Atala
- Wake Forest Institute for Regenerative Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA; (A.D.G.); (X.Z.)
| | - Yuanyuan Zhang
- Wake Forest Institute for Regenerative Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA; (A.D.G.); (X.Z.)
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22
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De Simone U, Caloni F, Pignatti P, Gaetano C, Locatelli CA, Coccini T. Human stromal cell-based protocol to generate astrocytes: a straightforward in vitro predictive strategy in neurotoxicology. Toxicol Mech Methods 2025; 35:340-355. [PMID: 39626968 DOI: 10.1080/15376516.2024.2435351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 11/22/2024] [Accepted: 11/23/2024] [Indexed: 05/04/2025]
Abstract
The inherent adaptability of human mesenchymal stromal cells (hMSCs) to differentiate into neural lineages provides a valuable resource for investigating potential neurotoxicity in humans. By harnessing the ability of hMSCs to transform into astrocytes, we can evaluate the effects of various agents on these vital cells. Our protocol employs hMSCs sourced from umbilical cord tissue, ensuring a readily available supply of high-quality cells. The hMSC-to-neural workflow encompasses six essential steps: hMSC culture, followed by the generation of embryoid bodies (EBs) from these cells on specialized surfaces. Next, EBs and cells are expanded in a growth-promoting medium, directing them toward neural lineages. Subsequent differentiation into immature astrocytes is achieved through the use of specific factors. The process continues with the maturation of EBs/cells into astrocyte-like cells (hALCs) under optimized conditions, culminating in the final development of hALCs in a specialized medium. This methodology yields cells that display astrocyte morphology and express characteristic markers such as GFAP and S100β. The protocol is efficient, requiring roughly 6 weeks to generate hALCs from primary hMSCs without genetic manipulation. The application of hMSCs in evaluating cell damage triggered by neurotoxicants like MeHg and MGO underscores their potential as a valuable component within a more extensive battery of neurotoxicity tests.
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Affiliation(s)
- Uliana De Simone
- Laboratory of Clinical and Experimental Toxicology, and Pavia Poison Center-National Toxicology Information Center, Toxicology Unit, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | - Francesca Caloni
- Dipartimento di Scienze e Politiche Ambientali (ESP), Università degli Studi di Milano, Milan, Italy
| | - Patrizia Pignatti
- Allergy and Immunology Unit, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | - Carlo Gaetano
- Laboratory of Epigenetics, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | - Carlo Alessandro Locatelli
- Laboratory of Clinical and Experimental Toxicology, and Pavia Poison Center-National Toxicology Information Center, Toxicology Unit, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | - Teresa Coccini
- Laboratory of Clinical and Experimental Toxicology, and Pavia Poison Center-National Toxicology Information Center, Toxicology Unit, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
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23
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Hetta HF, Elsaghir A, Sijercic VC, Ahmed AK, Gad SA, Zeleke MS, Alanazi FE, Ramadan YN. Clinical Progress in Mesenchymal Stem Cell Therapy: A Focus on Rheumatic Diseases. Immun Inflamm Dis 2025; 13:e70189. [PMID: 40353645 PMCID: PMC12067559 DOI: 10.1002/iid3.70189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 05/10/2024] [Accepted: 03/21/2025] [Indexed: 05/14/2025] Open
Abstract
BACKGROUND Rheumatic diseases are chronic immune-mediated disorders affecting multiple organ systems and significantly impairing patients' quality of life. Current treatments primarily provide symptomatic relief without offering a cure. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option due to their ability to differentiate into various cell types and their immunomodulatory, anti-inflammatory, and regenerative properties. This review aims to summarize the clinical progress of MSC therapy in rheumatic diseases, highlight key findings from preclinical and clinical studies, and discuss challenges and future directions. METHODOLOGY A comprehensive review of preclinical and clinical studies on MSC therapy in rheumatic diseases, including systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, osteoporosis, Sjögren's syndrome, Crohn's disease, fibromyalgia, systemic sclerosis, dermatomyositis, and polymyositis, was conducted. Emerging strategies to enhance MSC efficacy and overcome current limitations were also analyzed. RESULTS AND DISCUSSION Evidence from preclinical and clinical studies suggests that MSC therapy can reduce inflammation, modulate immune responses, and promote tissue repair in various rheumatic diseases. Clinical trials have demonstrated potential benefits, including symptom relief and disease progression delay. However, challenges such as variability in treatment response, optimal cell source and dosing, long-term safety concerns, and regulatory hurdles remain significant barriers to clinical translation. Standardized protocols and further research are required to optimize MSC application. CONCLUSION MSC therapy holds promise for managing rheumatic diseases, offering potential disease-modifying effects beyond conventional treatments. However, large-scale, well-controlled clinical trials are essential to establish efficacy, safety, and long-term therapeutic potential. Addressing current limitations through optimized treatment protocols and regulatory frameworks will be key to its successful integration into clinical practice.
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Affiliation(s)
- Helal F. Hetta
- Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of PharmacyUniversity of TabukTabukSaudi Arabia
| | - Alaa Elsaghir
- Department of Microbiology and Immunology, Faculty of PharmacyAssiut UniversityAssiutEgypt
| | | | - Abdulrahman K. Ahmed
- Emergency Medicine Unit, Department of Anaethesia and Intensive Care, Faculty of MedicineAssiut UniversityAssiutEgypt
| | - Sayed A. Gad
- Emergency Medicine Unit, Department of Anaethesia and Intensive Care, Faculty of MedicineAssiut UniversityAssiutEgypt
| | - Mahlet S. Zeleke
- Menelik II Medical and Health Science CollegeAddis AbabaEthiopia
| | - Fawaz E. Alanazi
- Department of Pharmacology and Toxicology, Faculty of PharmacyUniversity of TabukTabukSaudi Arabia
| | - Yasmin N. Ramadan
- Department of Microbiology and Immunology, Faculty of PharmacyAssiut UniversityAssiutEgypt
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24
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Wachtel N, Weber L, Moellhoff N, Kuhlmann C, Giunta RE, Alberton P, Ehrl D, Wiggenhauser S. Platelet-Rich Fibrin Mediates Beneficial Effects on Adipose-Derived Stem Cells via Increased Levels of Key Cytokines. Wound Repair Regen 2025; 33:e70040. [PMID: 40396345 DOI: 10.1111/wrr.70040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 04/11/2025] [Accepted: 04/29/2025] [Indexed: 05/22/2025]
Abstract
Recent studies showcased the regenerative potential of Platelet-Rich Fibrin (PRF) combined with Adipose-Derived Stem Cells (ASC). PRF enhances cellular proliferation through sustained growth factor secretion which are continuously released to surrounding cells. However, its regulatory mechanisms remain unclear. ASC were isolated from liposuction and abdominoplasty samples of healthy donors, characterised via flow-cytometry and cultured for 7 days. Four cell culture conditions were tested: (1) 10% PRF extract (PRFe), (2) 10% Platelet-Low Plasma (PLP), (3) 10% Foetal Bovine Serum (FBS) and (4) basal medium as control. Cell viability and proliferation were assessed using AlamarBlue and PicoGreen assays, as well as live-dead staining. Enzyme-Linked Immunosorbent Assays quantified growth factor concentrations, while multiplex qPCR and immunocytochemical staining analysed gene and protein expression on days 1 and 7. PRFe-supplemented cultures showed the highest viability and proliferation, significantly surpassing other groups at day 7 (p < 0.05). Supernatant analysis revealed significantly elevated TGF-β1 and PDGF-AA/BB levels in PRFe cultures at day 7 (p of at least < 0.05). Multiplex qPCR indicated increased expression of proliferation and pluripotency markers (NANOG, JUN, SOX2, RPS6KA4; p < 0.05) and fibrillar collagen (COL1A; p < 0.05) in the PRFe group. These findings demonstrate that PRFe significantly enhances ASC proliferation and regenerative potential. Elevated levels of TGF-1, PDGF-AA/BB and to a lesser extend VEGF in PRFe cultures suggest that its benefits in regenerative medicine may be linked to these cytokines' upregulation. These results underscore PRFe's potential as a key supplement for optimising ASC-based therapies in tissue regeneration.
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Affiliation(s)
- Nikolaus Wachtel
- Division of Hand, Plastic and Aesthetic Surgery, University Hospital, LMU Munich, Germany
| | - Luisa Weber
- Division of Hand, Plastic and Aesthetic Surgery, University Hospital, LMU Munich, Germany
| | - Nicholas Moellhoff
- Division of Hand, Plastic and Aesthetic Surgery, University Hospital, LMU Munich, Germany
| | - Constanze Kuhlmann
- Division of Hand, Plastic and Aesthetic Surgery, University Hospital, LMU Munich, Germany
| | - Riccardo E Giunta
- Division of Hand, Plastic and Aesthetic Surgery, University Hospital, LMU Munich, Germany
| | - Paolo Alberton
- Division of Hand, Plastic and Aesthetic Surgery, University Hospital, LMU Munich, Germany
| | - Denis Ehrl
- Division of Hand, Plastic and Aesthetic Surgery, University Hospital, LMU Munich, Germany
- Department of Plastic, Reconstructive and Hand Surgery, Burn Center for Severe Burn Injuries, Klinikum Nuremberg Hospital, Paracelsus Medical University, Germany
| | - Severin Wiggenhauser
- Division of Hand, Plastic and Aesthetic Surgery, University Hospital, LMU Munich, Germany
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25
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Rahmawati FN, Takakura N. Development and aging of resident endothelial stem cells in pre-existing blood vessels. Exp Hematol 2025:104795. [PMID: 40311858 DOI: 10.1016/j.exphem.2025.104795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 04/09/2025] [Accepted: 04/13/2025] [Indexed: 05/03/2025]
Abstract
Organ-specific somatic stem cells play an important role in supporting tissue turnover and facilitating regeneration on injury. Hematopoietic stem cells are one of the most established organ-specific somatic cells that have been frequently used for transplantation therapy. Recently, there has been a growing interest in other organ-specific somatic cells, including vascular endothelial stem cells (VESCs). We have previously reported on the use of CD157 and CD200 as markers to isolate VESCs from adult mouse organs, particularly the liver. In this review, we aimed to summarize, based on our previous research, how CD157⁺CD200⁺ VESCs in the liver develop from the fetal stage to postnatal life, what transcriptional regulatory mechanisms govern them, and how VESCs change with aging.
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Affiliation(s)
- Fitriana N Rahmawati
- Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
| | - Nobuyuki Takakura
- Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan; Center for Infectious Disease Education and Research, Osaka University, Suita, Osaka, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Osaka, Japan.
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26
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Muslem S, AlTurani M, Maqsood MB, Qaseer MA. Cardiac Repair and Clinical Outcomes of Stem Cell Therapy in Heart Failure: A Systematic Review and Meta-Analysis. Diseases 2025; 13:136. [PMID: 40422568 DOI: 10.3390/diseases13050136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 04/17/2025] [Accepted: 04/18/2025] [Indexed: 05/28/2025] Open
Abstract
BACKGROUND While heart failure with reduced ejection fraction (HFrEF) remains a major global health burden, mesenchymal stem cell (MSC) therapy has emerged as a promising intervention designed to improve cardiac function and reduce morbidity among patients unresponsive to conventional treatments. MSC therapy has shown promise by targeting left ventricular pressure and improving wall thickness, contributing to reductions in HF-related morbidity and mortality rates. This systematic review and meta-analysis bridges a gap in current research through a focused examination of the most recent clinical trials to cohesively assess MSC therapy in HFrEF patients. METHODS We conducted a systematic review and meta-analysis of clinical trials published from 2018 onwards, which were obtained from multiple databases such as PUBMED, Scopus, EBSCO Medline, EBSCO CINAHL Science Direct, and the Cochrane Library. This review investigates the efficacy and safety outcomes of MSC therapy in patients above 18 years of age with a known diagnosis of heart failure with a reduced ejection fraction (HFrEF). The primary outcome was the change in the left ventricular ejection fraction (LVEF). Secondary outcomes encompassed several efficacy outcomes, such as Global Circumferential strain (GCS), the 6-Minute Walk Test (6MWT), Quality of Life (QoL), and major adverse cardiac events (MACE). A PRISMA flow diagram was constructed to illustrate the identification, screening, eligibility, and inclusion of studies at each stage of the review process. RESULTS A total of 330 studies were initially identified, but only 12 met the inclusion criteria. MSC therapy resulted in a small, non-significant improvement in LVEF (Hedges' g = 0.096, p = 0.18) with low heterogeneity (I² = 0.5%). Only QoL showed significant improvement (Hedges' g = -0.518, p = 0.01). No significant changes in other efficacy outcomes were observed. The therapy was not associated with an increased risk of MACE. CONCLUSION While MSC therapy was safe and improved QoL for HFrEF patients, it did not significantly improve LVEF or other efficacy outcomes. Further large-scale, standardized trials are required to better understand the potential role of MSCs in heart failure (HF) therapy.
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Affiliation(s)
- Salman Muslem
- Salmaniya Medical Complex, Manama P.O. Box 11190, Bahrain
| | - Mariam AlTurani
- Royal College of Surgeons, Ireland-Medical University of Bahrain, Manama P.O. Box 15503, Bahrain
| | | | - Maryam Al Qaseer
- Department of Cardiology, King Fahad Specialist Hospital, Eastern Health Cluster, Dammam 32253, Saudi Arabia
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Fu L, Pelosini L, Kopsachilis N, Foti R, D'Esposito F, Musa M, D'Amico A, Tognetto D, Gagliano C, Zeppieri M. Evaluating the efficacy of stem cells in treating severe dry eye disease. World J Stem Cells 2025; 17:101891. [PMID: 40308890 PMCID: PMC12038461 DOI: 10.4252/wjsc.v17.i4.101891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 02/17/2025] [Accepted: 03/21/2025] [Indexed: 04/23/2025] Open
Abstract
Dry eye disease (DED) is a multifactorial disorder that disturbs ocular surface equilibrium, considerably diminishing quality of life. Present therapies only offer symptomatic alleviation. Stem cell treatment, especially mesenchymal stem cells (MSCs), has surfaced as a viable approach for tissue regeneration and immunological regulation in DED. Preclinical and early clinical investigations indicate that MSCs can improve lacrimal gland functionality, diminish inflammation, and facilitate corneal regeneration. Nonetheless, obstacles persist in enhancing MSC viability, determining the optimal MSC source, and guaranteeing sustained therapeutic effectiveness. Additional extensive randomized clinical trials are required to confirm the efficacy of MSC-based therapies for severe DED.
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Affiliation(s)
- Lanxing Fu
- Department of Ophthalmology, East Kent Hospitals University NHS Foundation Trust, Canterbury CT1 3NG, United Kingdom
| | - Lucia Pelosini
- Department of Ophthalmology, King's College Hospital NHS Foundation Trust, London SE5 9RS, United Kingdom
| | - Nick Kopsachilis
- Department of Ophthalmology, East Kent Hospitals University NHS Foundation Trust, Canterbury CT1 3NG, United Kingdom
| | - Roberta Foti
- Division of Rheumatology, A.O.U. "Policlinico-San Marco," Catania 95123, Italy
| | - Fabiana D'Esposito
- Imperial College Ophthalmic Research Group Unit, Imperial College, London NW1 5QH, United Kingdom
- Department of Neurosciences, Reproductive Sciences and Dentistry, University of Naples Federico II, Via Pansini 5, 80131 Napoli, Italy
| | - Mutali Musa
- Department of Optometry, University of Benin, Benin 300283, Nigeria
- Department of Ophthalmology, Centre for Sight Africa, Nkpor, Onitsha 434112, Nigeria
| | - Alberto D'Amico
- Academic Neurosurgery, Department of Neurosciences, University of Padova, Padova 35128, Italy
| | - Daniele Tognetto
- Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste 34129, Italy
| | - Caterina Gagliano
- Department of Medicine and Surgery, University of Enna "Kore," Catania 94100, Italy
- Mediterranean Foundation "G.B. Morgagni", 95125 Catania, Italy
| | - Marco Zeppieri
- Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste 34129, Italy
- Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy.
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28
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Ma Y, Song B, Peng J, Wei F, Hao Y, Wen Y, Lv H, Shi X, Wang Y, Peng T. Cornua cervi degelatinatum inhibits breast cancer stem-like cell properties and metastasis via miR-148a-3p-mediated TGF-β/Smad2 pathway. JOURNAL OF ETHNOPHARMACOLOGY 2025; 346:119709. [PMID: 40157402 DOI: 10.1016/j.jep.2025.119709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 03/12/2025] [Accepted: 03/25/2025] [Indexed: 04/01/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Cornua cervi degelatinatum (CCD) is formed by removing the gelatinous substance from deer antlers according to traditional methods. It was first recorded in the Shennong's Classic of Materia Medica and has been included in the Pharmacopoeia of the People's Republic of China. It is commonly used in clinical practice for the treatment of diseases such as cancer and infertility. AIM OF THE STUDY This study aims to investigate the impact of CCD aqueous extract on the proliferation and stemness of breast cancer (BC) cells, with an emphasis on its regulation of miR-148a-3p expression and associated molecular pathways. MATERIALS AND METHODS Breast cancer cells were treated with various concentrations of CCD to assess its effects on cancer stem cell (CSC) features, epithelial-mesenchymal transition (EMT) markers, and overall plasticity. The UALCAN platform was utilized to analyze the relationship between miR-148a-3p and Smad2 expression. Functional experiments involving miR-148a-3p overexpression were performed to elucidate CCD's modulatory effects on the TGF-β/Smad2 pathway. Furthermore, molecular docking analysis was conducted to predict the binding affinity of CCD's active components to Smad2. RESULTS The CCD aqueous extract significantly reduced BC cell viability in vitro and dose-dependently suppressed the expression of stemness- and EMT-related proteins. Bioinformatics analysis and luciferase reporter assays validated miR-148a-3p as a direct regulator of Smad2, inhibiting the TGF-β/Smad2 signaling pathway. Molecular docking revealed strong binding interactions between CCD's active components and Smad2. CONCLUSIONS CCD exhibits anti-BC effects by working synergistically with miR-148a-3p to inhibit the TGF-β/Smad2 pathway, thereby reducing BC stemness and EMT progression. These findings provide valuable insights into the molecular mechanisms underlying CCD's therapeutic potential in BC treatment.
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Affiliation(s)
- Yanmiao Ma
- College of Basic Medical Sciences, Shanxi University of Chinese Medicine, Taiyuan, 030619, China; Shanxi Provincial Key Laboratory of Classical Prescription Strengthening Yang, Taiyuan, 030013, China; Shanxi Provincial Key Laboratory of Prescription Compatibility and Functions, Taiyuan, 030619, China.
| | - Bo Song
- College of Third Clinical Medicine, Shanxi University of Chinese Medicine, Taiyuan, 030619, China
| | - Jiehao Peng
- College of Third Clinical Medicine, Shanxi University of Chinese Medicine, Taiyuan, 030619, China
| | - Fuxia Wei
- College of Third Clinical Medicine, Shanxi University of Chinese Medicine, Taiyuan, 030619, China
| | - Yuanhui Hao
- College of Third Clinical Medicine, Shanxi University of Chinese Medicine, Taiyuan, 030619, China
| | - Ya Wen
- College of First Clinical Medicine, Shanxi University of Chinese Medicine, Taiyuan, 030619, China
| | - Huiling Lv
- Experimental Management Center, Shanxi University of Chinese Medicine, Taiyuan, 030619, China
| | - Xiaoli Shi
- Department of Rehabilitation, Shanxi Acupuncture Hospital, Taiyuan, 030006, China
| | - Yonghui Wang
- College of Basic Medical Sciences, Shanxi University of Chinese Medicine, Taiyuan, 030619, China; Shanxi Provincial Key Laboratory of Classical Prescription Strengthening Yang, Taiyuan, 030013, China.
| | - Tao Peng
- Shanxi Hospital of Integrated Traditional Chinese and Western Medicine, Taiyuan, 030013, China; Shanxi Provincial Key Laboratory of Classical Prescription Strengthening Yang, Taiyuan, 030013, China; Shanxi Provincial Key Laboratory of Prescription Compatibility and Functions, Taiyuan, 030619, China.
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Karam M, Aqel S, Haider MZ, Fathima A, Charafedine A, Daher MA, Shaito A, El-Sabban M, Saliba J. Beyond the Injury: How Does Smoking Impair Stem Cell-Mediated Repair Mechanisms? A Dual Review of Smoking-Induced Stem Cell Damage and Stem Cell-Based Therapeutic Applications. Stem Cell Rev Rep 2025:10.1007/s12015-025-10886-9. [PMID: 40279029 DOI: 10.1007/s12015-025-10886-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/14/2025] [Indexed: 04/26/2025]
Abstract
While the literature on molecular and clinical effects of smoking on the lungs and other organs has been expansively reviewed, there is no comprehensive compilation of the effects of smoking on stem cell (SC) populations. Recent research has shown that tobacco exposure severely compromises the function of SC populations, particularly those involved in tissue regeneration: mesenchymal SCs (MSCs), neural progenitors, and hematopoietic SCs. SC-based therapies have emerged as a promising approach to counteract smoking-related damage. In particular, MSCs have been extensively studied for their immunomodulatory properties, demonstrating the ability to repair damaged tissues, reduce inflammation, and slow disease progression in conditions such as chronic obstructive pulmonary disease. Combination therapies, which integrate pharmaceuticals with SC treatments, have shown potential in enhancing regenerative outcomes. This review examines the impact of smoking on SC biology, describes the processes impairing SC-mediated repair mechanisms and highlights recent advancements in SC-based therapies in the treatment of smoking-induced diseases. This review has two prongs: (1) it attempts to explain potential smoking-related disease etiology, and (2) it addresses a gap in the literature on SC-mediated repair mechanisms in chronic smokers.
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Affiliation(s)
- Mario Karam
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
- Department of Translational Cancer Medicine, Faculty of Medicine, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8, 00290, Helsinki, Helsinki, Finland
| | - Sarah Aqel
- Medical Research Center, Hamad Medical Corporation, Doha, Qatar
| | - Mohammad Z Haider
- Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar
| | - Aseela Fathima
- Biomedical Research Center and Department of Biomedical Sciences at College of Health Sciences, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar
| | - Adib Charafedine
- College Of Pharmacy, American University of Iraq-Baghdad, Baghdad, Iraq
| | - Mira Abou Daher
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
- Department of Public Health, Faculty of Health Sciences, University of Balamand, Sin El Fil, PO Box: 55251, Beirut, Lebanon
| | - Abdullah Shaito
- Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar
- Biomedical Research Center and Department of Biomedical Sciences at College of Health Sciences, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar
| | - Marwan El-Sabban
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Jessica Saliba
- Department of Public Health, Faculty of Health Sciences, University of Balamand, Sin El Fil, PO Box: 55251, Beirut, Lebanon.
- Department of Biology, Faculty of Science, Lebanese University, Beirut, Lebanon.
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30
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Solomon AD, Dabral S, Brajesh RG, Day BW, Juric M, Zielonka J, Bosnjak ZJ, Pant T. Understanding the Mechanisms of Chemotherapy-Related Cardiotoxicity Employing hiPSC-Derived Cardiomyocyte Models for Drug Screening and the Identification of Genetic and Epigenetic Variants. Int J Mol Sci 2025; 26:3966. [PMID: 40362211 PMCID: PMC12071959 DOI: 10.3390/ijms26093966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2025] [Revised: 04/10/2025] [Accepted: 04/18/2025] [Indexed: 05/15/2025] Open
Abstract
Chemotherapy-related cardiotoxicity (CTRTOX) is a profound and common side effect of cancer-based therapy in a subset of patients. The underlying factors and the associated mechanisms contributing to severe toxicity of the heart among these patients remain unknown. While challenges remain in accessing human subjects and their ventricular cardiomyocytes (CMs), advancements in human induced pluripotent stem cell (hiPSC)-technology-based CM differentiation protocols over the past few decades have paved the path for iPSC-based models of human cardiac diseases. Here, we offer a detailed analysis of the underlying mechanisms of CTRTOX. We also discuss the recent advances in therapeutic strategies in different animal models and clinical trials. Furthermore, we explore the prospects of iPSC-based models for identifying novel functional targets and developing safer chemotherapy regimens for cancer patients that may be beneficial for developing personalized cardioprotectants and their application in clinical practice.
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Affiliation(s)
- Abhishikt David Solomon
- Adams School of Dentistry, Oral and Craniofacial Biomedicine, University of North Carolina, Chapel Hill, NC 27599, USA;
| | - Swarna Dabral
- Maharishi Markandeshwar College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala 133207, India;
| | - Raman Gulab Brajesh
- Department of Biomedical Engineering and Bioinformatics, Swami Vivekanand Technical University, Durg 491107, India;
| | | | - Matea Juric
- Department of Biophysics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA; (M.J.); (J.Z.)
| | - Jacek Zielonka
- Department of Biophysics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA; (M.J.); (J.Z.)
| | - Zeljko J. Bosnjak
- Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA;
| | - Tarun Pant
- Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA;
- Department of Surgery, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
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31
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Budi HS, Handajani J, Amir LR, Soekanto SA, Ulfa NM, Wulansari SA, Shen YK, Yamada S. Nanoemulgel Development of Stem Cells from Human Exfoliated Deciduous Teeth-Derived Conditioned Medium as a Novel Nanocarrier Growth Factors. Eur J Dent 2025. [PMID: 40267955 DOI: 10.1055/s-0045-1806963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/25/2025] Open
Abstract
OBJECTIVE We aimed to develop a nanoemulgel of stem cells from human exfoliated deciduous teeth-derived conditioned medium (SHED-CM) for oral wound biotherapy candidate. MATERIALS AND METHODS Deciduous tooth pulp was collected from two patients aged 6 years. The mesenchymal stem cell marker expression was analyzed by immunocytochemistry of CD45, CD90, and CD105. Alizarin red staining was performed to differentiate SHEDs from osteoblasts. The quantitative and quantification of transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF) secreted into conditioned media were measured using sodium dodecyl sulfate polyacrylamide gel electrophoresis and enzyme-linked immunosorbent assay. The characteristics of the nanoemulgel of SHED-CM (NESCM) were analyzed in terms of organoleptic properties, pH, and homogeneity. The cytotoxicity of NESCM 1.5% was analyzed in human gingival fibroblast (hGF) cell and osteoblast cell line (MC3T3) by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay. STATISTICAL ANALYSIS The results were presented as mean ± standard deviation (X ± SD), and the differences between groups were analyzed using the post hoc Tukey's test at a significance level of p-value < 0.05. RESULTS SHEDs were successfully isolated, which were characterized for positive marker expressions of CD90 and CD105 and negative expression of CD45 as well as their osteogenic commitment. In SHED-CM, TGF-β and VEGF were detected on day 1 of conditioning and afterward. Notably, the growth factor enriched as the duration of conditioning increased. The generated nanoemulgel with SHED-CM was stable and homogeneous, and had limited cytotoxic effects on hGF and MC3T3 cell culture. CONCLUSION SHED-CM containing the growth factors can potentially be used as oral wound biotherapy in the form of nanoemulgel.
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Affiliation(s)
- Hendrik Setia Budi
- Department of Oral Biology, Dental Pharmacology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
- Cell and Biology Research, Surabaya Science Laboratory, Surabaya, Indonesia
| | - Juni Handajani
- Department of Oral Biology, Faculty of Dentistry, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Lisa Rinanda Amir
- Department of Oral Biology, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia
| | - Sri Angky Soekanto
- Department of Oral Biology, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia
| | - Ninik Mas Ulfa
- Department of Pharmaceutica, Pharmacology and Clinical Pharmacy, Surabaya Pharmacy Academy, Surabaya, Indonesia
| | - Silvi Ayu Wulansari
- Department of Pharmaceutica, Pharmacology and Clinical Pharmacy, Surabaya Pharmacy Academy, Surabaya, Indonesia
| | - Yung-Kang Shen
- School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
| | - Shuntaro Yamada
- Center of Translational Oral Research, University of Bergen, Bergen, Norway
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32
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Sulaiman S, Alaarag A, Rayyan N, Tuffaha Y, Al-Awamleh N, Al Dojan KA. Advancing toward a curative frontier: an updated narrative review on stem-cell therapy in pediatric type 1 diabetes. World J Pediatr 2025:10.1007/s12519-025-00908-4. [PMID: 40257724 DOI: 10.1007/s12519-025-00908-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 03/28/2025] [Accepted: 03/31/2025] [Indexed: 04/22/2025]
Abstract
BACKGROUND Type 1 diabetes (T1D) is a chronic autoimmune disease primarily diagnosed in childhood, characterized by pancreatic β-cell destruction, severe insulin deficiency, and hyperglycemia. Current treatments, including insulin therapy and glucose-lowering medications, manage the condition but fall short of offering a cure. In this review we explore the potential of stem-cell therapy as a transformative and curative approach for T1D, focusing on its promise in regenerating β-cells and addressing challenges specific to the pediatric population. DATA SOURCES A comprehensive review of the literature was conducted to evaluate stem-cell types: embryonic, perinatal, adult, induced pluripotent and cancer stem cells, and their role in T1D treatment. Particular emphasis was placed on methods for β-cell differentiation, advancements in autologous and allogeneic stem-cell transplantation and emerging strategies to overcome safety, efficacy, and economic barriers. Challenges such as immune rejection, tumorigenicity, and cost-effectiveness were analyzed, alongside novel solutions like immune-shielding and clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 (Cas9) technology. RESULTS Stem-cell therapy presents a promising avenue for curing T1D, offering potential for β-cell regeneration and reduced dependence on exogenous insulin. However, challenges such as delayed β-cell functionality, immune responses, tumor risks, and high costs hinder widespread application. CONCLUSIONS Advancements in personalized medicine, immune-shielding strategies, and cost reduction may pave the way for clinical success, especially in pediatric populations. Further research addressing these barriers is essential to establish stem-cell therapy as a viable and equitable treatment option.
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Affiliation(s)
- Samia Sulaiman
- School of Medicine, University of Jordan, Amman, Jordan.
| | | | - Nadin Rayyan
- School of Medicine, University of Jordan, Amman, Jordan
| | | | | | - Khalid Adel Al Dojan
- Department of General Pediatrics, Maternity and Children's Hospital, Bashir Hospital, Ministry of Health Basheer Hospitals, Amman, Jordan
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Wei H, Kappler C, Green E, Jiang H, Yeung T, Wang H. GRP94 is indispensable for definitive endoderm specification of human induced pluripotent stem cells. Mol Ther 2025:S1525-0016(25)00299-0. [PMID: 40254879 DOI: 10.1016/j.ymthe.2025.04.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Revised: 03/24/2025] [Accepted: 04/16/2025] [Indexed: 04/22/2025] Open
Abstract
Human induced pluripotent stem cell (hiPSC)-derived insulin-producing β cell therapy shows promise in treating type 1 diabetes and potentially type 2 diabetes. Understanding the genetic factors controlling hiPSC differentiation could optimize this therapy. In this study, we investigated the role of glucose-regulated protein 94 (GRP94) in human β cell development by generating HSP90B1/GRP94 knockout (KO) hiPSCs, re-expressing GRP94 in the mutants and inducing their β cell differentiation. Our results revealed that GRP94 depletion hindered β cell generation by promoting cell death induced by endoplasmic reticulum (ER) stress and other stressors during definitive endoderm (DE) differentiation. Moreover, GRP94 deletion resulted in decreased activation of WNT/β-catenin signaling, which is critical for DE specification. Re-expression of GRP94 in GRP94 KO iPSCs partially reversed DE differentiation deficiency and alleviated cell death. These findings highlight the previously unrecognized indispensable role of GRP94 in human DE formation and consequent β cell development from hiPSCs. GRP94 mitigates ER stress-induced cell death and regulates the WNT/β-catenin signaling pathway, which is both crucial for successful β cell differentiation. These results provide new insights into the molecular mechanisms underlying β cell differentiation from hiPSCs and suggest that targeting GRP94 pathways could enhance the efficiency of hiPSC-derived insulin-producing cell therapies for diabetes treatment.
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Affiliation(s)
- Hua Wei
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
| | - Christiana Kappler
- Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA
| | - Erica Green
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
| | - Hanna Jiang
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
| | - Tiffany Yeung
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
| | - Hongjun Wang
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA; Ralph H Johnson VA Medical Center, Charleston, SC, USA.
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Liu S, Liu W, Liu Y, Luo D, Feng J, Hou L, Cui H, Liu Y, Chen X, Zhu X, Wei L, Lv Q, Zhang Z. Repair effect of adipose-derived mesenchymal stem cell-conditioned medium on cyclophosphamide-induced ovarian injury in mice. Reprod Toxicol 2025; 135:108923. [PMID: 40254105 DOI: 10.1016/j.reprotox.2025.108923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Revised: 04/02/2025] [Accepted: 04/15/2025] [Indexed: 04/22/2025]
Abstract
The chemotherapeutic drug cyclophosphamide (CTX) may damage the ovarian tissue of females and induce premature ovarian insufficiency (POI). This study aimed to investigate the therapeutic effect of adipose-derived mesenchymal stem cell-conditioned medium (ADSC-CM) on CTX-induced POI mice, and to provide new support for the clinical use of cell-free therapy for POI. Female mice were treated with CTX intraperitoneal injection for 2 weeks, followed by ADSCs or ADSC-CM by intravenous injection for 2 weeks. At the end of the experiment, various parameters were assessed, including ovarian interstitial fibrosis, cell proliferation, follicular count, the levels of follicle-stimulating hormone (FSH) and estradiol (E2), and the expression of gonadal hormone receptor. Additionally, we assessed the levels of oxidative stress, apoptosis, and apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal kinase (JNK) signaling pathway-related proteins and genes in ovarian tissue. The results showed that ADSCs or ADSC-CM treatment reduced ovarian interstitial fibrosis, promoted the proliferation of cells in the follicles, and increased the number of follicles and ovarian function. In addition, ADSCs and ADSC-CM also reduced the levels of ovarian oxidative stress, decreased the apoptosis of granulosa cells (GCs), and inhibited the activation of ASK1/JNK signaling pathway. In conclusion, our study confirmed that ADSC-CM, like ADSCs, could exert therapeutic effects in POI diseases, and the underlying mechanism may be related to the inhibition of oxidative stress-mediated activation of ASK1/JNK signaling pathway. This study has important implications for the development of cell-free therapies for the clinical treatment of POI diseases.
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Affiliation(s)
- Shuangjuan Liu
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China.
| | - Weiqi Liu
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China.
| | - Yumei Liu
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China.
| | - Dongliu Luo
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China.
| | - Jingwen Feng
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China.
| | - Leyao Hou
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China.
| | - Haotong Cui
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China.
| | - Yao Liu
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China.
| | - Xiaoguang Chen
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China.
| | - Xuemin Zhu
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China.
| | - Lan Wei
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China.
| | - Qiongxia Lv
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China.
| | - Ziqiang Zhang
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China.
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Xue B, Xu Z, Li L, Guo K, Mi J, Wu H, Li Y, Xie C, Jin J, Xu J, Jiang C, Gu X, Qin M, Jiang Q, Cao Y, Wang W. Hydrogels with programmed spatiotemporal mechanical cues for stem cell-assisted bone regeneration. Nat Commun 2025; 16:3633. [PMID: 40240370 PMCID: PMC12003706 DOI: 10.1038/s41467-025-59016-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Accepted: 04/08/2025] [Indexed: 04/18/2025] Open
Abstract
Hydrogels are extensively utilized in stem cell-based tissue regeneration, providing a supportive environment that facilitates cell survival, differentiation, and integration with surrounding tissues. However, designing hydrogels for regenerating hard tissues like bone presents significant challenges. Here, we introduce macroporous hydrogels with spatiotemporally programmed mechanical properties for stem cell-driven bone regeneration. Using liquid-liquid phase separation and interfacial supramolecular self-assembly of protein fibres, the macroporous structure of hydrogels provide ample space to prevent contact inhibition during proliferation. The rigid protein fibre-coated pore shell provides sustained mechanical cues for guiding osteodifferentiation and protecting against mechanical loads. Temporally, the hydrogel exhibits tunable degradation rates that can synchronize with new tissue deposition to some extent. By integrating localized mechanical heterogeneity, macroporous structures, surface chemistry, and regenerative degradability, we demonstrate the efficacy of these stem cell-encapsulated hydrogels in rabbit and porcine models. This marks a substantial advancement in tailoring the mechanical properties of hydrogels for stem cell-assisted tissue regeneration.
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Affiliation(s)
- Bin Xue
- Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, China.
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan, China.
- Institute for Brain Sciences, Nanjing University, Nanjing, China.
| | - Zhengyu Xu
- Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, China
- Chemistry and Biomedicine Innovation Center (ChemBIC), MOE Key Laboratory of High Performance Polymer Materials and Technology, and State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China
| | - Lan Li
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
- Jiangsu Engineering Research Center for 3D Bioprinting, Nanjing, China
| | - Kaiqiang Guo
- Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, China
| | - Jing Mi
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Haipeng Wu
- Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, China
| | - Yiran Li
- Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, China
| | - Chunmei Xie
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Jing Jin
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Juan Xu
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Chunping Jiang
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan, China
| | - Xiaosong Gu
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan, China
| | - Meng Qin
- Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, China
| | - Qing Jiang
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
- Jiangsu Engineering Research Center for 3D Bioprinting, Nanjing, China.
| | - Yi Cao
- Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, China.
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan, China.
- Institute for Brain Sciences, Nanjing University, Nanjing, China.
- Chemistry and Biomedicine Innovation Center (ChemBIC), MOE Key Laboratory of High Performance Polymer Materials and Technology, and State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.
| | - Wei Wang
- Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, China.
- Institute for Brain Sciences, Nanjing University, Nanjing, China.
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Caravia LG, Mitranovici MI, Oala IE, Tiron AT, Simionescu AA, Borcan AM, Craina M. The Importance of Cancer Stem Cells and Their Pathways in Endometrial Cancer: A Narrative Review. Cells 2025; 14:594. [PMID: 40277919 PMCID: PMC12025850 DOI: 10.3390/cells14080594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2025] [Revised: 03/25/2025] [Accepted: 04/09/2025] [Indexed: 04/26/2025] Open
Abstract
Endometrial cancer is one of the most common malignancies seen in women in developed countries. While patients in the early stages of this cancer show better responses to surgery, adjuvant hormonal therapy, and chemotherapy, patients with recurrence show treatment resistance. Researchers have recently focused on cancer stem cells (CSCs) in the treatment of gynecologic cancer in general but also specifically in endometrial cancer. CSCs have been investigated because of their resistance to conventional therapies, such as chemo- and radiotherapy, and their ability to induce the progression and recurrence of malignancy. The activation of alternative pathways, such as WNT, PI3K, NF-kB, or NOTCH, could be the basis of the acquisition of these abilities of CSCs. Their specific markers and signaling pathways could be treatment targets for CSCs. In this article, we discuss the importance of obtaining a better understanding of the molecular basis and pathways of CSCs in endometrial cancer and the role of CSCs, aiming to discover more specific therapeutic approaches.
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Affiliation(s)
- Laura Georgiana Caravia
- Division of Cellular and Molecular Biology and Histology, Department of Morphological Sciences, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Melinda Ildiko Mitranovici
- Public Health Department, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology, 540142 Targu Mures, Romania
| | - Ioan Emilian Oala
- Department of Obstetrics and Gynecology, Emergency County Hospital Hunedoara, 14 Victoriei Street, 331057 Hunedoara, Romania;
| | - Andreea Taisia Tiron
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Anca Angela Simionescu
- Department of Obstretics and Gynecology, Filantropia, Faculty of Medicine Carol Davila, 011171 Bucharest, Romania;
| | - Alina Maria Borcan
- Department of Microbiology, National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Faculty of Medicine Carol Davila, 021105 Bucharest, Romania;
| | - Marius Craina
- Department of Obstetrics and Gynecology, “Victor Babes” University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania;
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Carpena NT, Chang SY, Mun S, Kim KW, Yoon HC, Chung PS, Mo JH, Ahn JC, Park JO, Han K, Choi JE, Jung JY, Lee MY. Shh agonist enhances maturation in homotypic Lgr5-positive inner ear organoids. Theranostics 2025; 15:5543-5565. [PMID: 40365278 PMCID: PMC12068299 DOI: 10.7150/thno.107345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Accepted: 04/07/2025] [Indexed: 05/15/2025] Open
Abstract
Background: The regeneration of functional hair cells (HCs) remains a critical challenge in addressing sensorineural hearing loss. This study aimed to investigate the molecular and functional mechanisms driving stereocilia maturation within inner ear organoids (IEO) derived from homogenic Lgr5-positive progenitor cells (LPCs) and to compare outcomes with traditional heterotypic cultures. Methods: Mouse cochlear LPCs were isolated via magnetic-activated cell sorting (MACS) to establish homotypic cultures, ensuring purity and eliminating the heterotypic influences present in traditional manual isolation (MI) methods. Differentiation into HCs was induced through Wnt and Notch signaling modulation. Transcriptomic profiling using bulk and single-cell RNA sequencing (scRNA-seq) identified gene expression changes linked to stereocilia development. A Sonic Hedgehog (Shh) agonist was applied to enhance structural maturation of HCs. Functional assessment included electron microscopy, FM1-43 uptake assays, and microelectrode array recordings in assembloids of IEO with primary spiral ganglion neurons (SGN) co-cultures. Results: While homotypic LPC-derived IEOs successfully differentiated into HC-like cells, initial morphological assessment revealed immature stereocilia structures. Bulk RNA-seq analysis highlighted a downregulation of morphogenesis-related genes in these organoids. The application of a Shh agonist, acting as a key morphogen, promoted stereocilia development, as evidenced by enhanced ultrastructural features and increased expression of cuticular plate-associated genes (Pls1, Lmo7 and Lrba). Single-cell RNA sequencing (scRNA-seq) further identified distinct cell clusters, which exhibited robust expression of stereocilia-related genes (Espn, Lhfpl5, Loxhd1 and Tmc1), indicative of advanced HC maturation. Electrophysiological assessments of IEO-SGN assembloids using microelectrode arrays confirmed functional mechanoelectrical transduction between cells. Conclusion: This integrated approach elucidates critical pathways and cellular dynamics underpinning stereocilia maturation and functional HC development in EIOs. These findings provide new insights into the molecular regulation of HC maturation and support the utility of Shh-modulated IEOs as a promising platform for inner ear regeneration and therapeutic development for inner ear regenerative therapies.
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Affiliation(s)
- Nathaniel T Carpena
- Department of Medical Laser, Graduate School of Medicine, Dankook University, Cheonan 31116, Republic of Korea
| | - So-Young Chang
- Beckman Laser Institute Korea, Dankook University, Cheonan 31116, Republic of Korea
| | - Seyoung Mun
- Department of Cosmedical & Materials, Dankook University, Cheonan 31116, Republic of Korea
| | - Kyung Wook Kim
- Department of Orthopaedic Surgery, Dankook University Hospital, Dankook University College of Medicine, Cheonan, 31116, Korea
| | - Hyun C Yoon
- Department of Molecular Science & Technology, Ajou University, Suwon, 443749, Republic of Korea
| | - Phil-Sang Chung
- Beckman Laser Institute Korea, Dankook University, Cheonan 31116, Republic of Korea
- Department of Otolaryngology-Head & Neck Surgery, College of Medicine, Dankook University, Cheonan 31116, Republic of Korea
| | - Ji-Hun Mo
- Department of Otolaryngology-Head & Neck Surgery, College of Medicine, Dankook University, Cheonan 31116, Republic of Korea
| | - Jin-Chul Ahn
- Beckman Laser Institute Korea, Dankook University, Cheonan 31116, Republic of Korea
- Medical Laser Research Center, Dankook University, Cheonan 31116, Republic of Korea
| | - Ji On Park
- Medical Laser Research Center, Dankook University, Cheonan 31116, Republic of Korea
| | - Kyudong Han
- Department of Microbiology, College of Science & Technology, Dankook University, Cheonan 31116, Republic of Korea
| | - Ji Eun Choi
- Department of Otolaryngology-Head & Neck Surgery, College of Medicine, Dankook University, Cheonan 31116, Republic of Korea
| | - Jae Yun Jung
- Department of Otolaryngology-Head & Neck Surgery, College of Medicine, Dankook University, Cheonan 31116, Republic of Korea
| | - Min Young Lee
- Beckman Laser Institute Korea, Dankook University, Cheonan 31116, Republic of Korea
- Department of Otolaryngology-Head & Neck Surgery, College of Medicine, Dankook University, Cheonan 31116, Republic of Korea
- Medical Laser Research Center, Dankook University, Cheonan 31116, Republic of Korea
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Nunes ADC, Pitcher LE, Exner HA, Grassi DJ, Burns B, Sanchez MBH, Tetta C, Camussi G, Robbins PD. Attenuation of Cellular Senescence and Improvement of Osteogenic Differentiation Capacity of Human Liver Stem Cells Using Specific Senomorphic and Senolytic Agents. Stem Cell Rev Rep 2025:10.1007/s12015-025-10876-x. [PMID: 40220121 DOI: 10.1007/s12015-025-10876-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/02/2025] [Indexed: 04/14/2025]
Abstract
Expansion of adult stem cells in culture increases the percent of senescent cells, reduces their differentiation capacity and limits their clinical use. Here, we investigated whether treatment with certain senotherapeutic drugs would reduce the accumulation of senescent cells during expansion of human liver stem cells (HLSCs) while maintaining their differentiation capacity. Our results demonstrate that chronic treatment with the senomorphic XJB-5-131 or the senolytics cocktail D + Q reduced the number of senescent cells and significantly reduced the expression of senescence-associated genes and several inflammatory SASP factors in later passage HLSCs. Additionally, treatment with XJB-5-131 and D + Q improved the capacity of HLSCs to undergo osteogenic differentiation following extensive in vitro expansion. Overall, our data demonstrate that treatment with XJB-5-13 or D + Q results in a reduction in the percentage of replication-induced senescent HLSCs and likely other types of adult stem cells and improve the potential therapeutic use of later passage human stem cells.
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Affiliation(s)
- Allancer D C Nunes
- Masonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA
| | - Louise E Pitcher
- Masonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA
| | - Henry A Exner
- Masonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA
| | | | - Brittan Burns
- Masonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA
| | - Maria Beatriz Herrera Sanchez
- Molecular Biotechnology Centre, University of Torino, Torino, Italy
- 2i3T Societ Per la Gestione Dell'incubatore di Imprese e per il Trasferimento Tecnologico Scarl, University of Torino, Torino, Italy
| | | | - Giovanni Camussi
- Molecular Biotechnology Centre, University of Torino, Torino, Italy
- Department of Medical Sciences, University of Torino, Torino, Italy
| | - Paul D Robbins
- Masonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.
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Liang Z, Xie H, Wu D. Immune mediated inflammatory diseases: moving from targeted biologic therapy, stem cell therapy to targeted cell therapy. Front Immunol 2025; 16:1520063. [PMID: 40260258 PMCID: PMC12009864 DOI: 10.3389/fimmu.2025.1520063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 03/13/2025] [Indexed: 04/23/2025] Open
Abstract
Despite the advancements in targeted biologic therapy for immune-mediated inflammatory diseases (IMIDs), significant challenges persist, including challenges in drug maintenance, primary and secondary non-responses, and adverse effects. Recent data have strengthened the evidence supporting stem cell therapy as an experimental salvage therapy into a standard treatment option. Recent preclinical and clinical studies suggested that chimeric antigen receptor T cell (CAR-T) therapy, which depleting tissue and bone marrow B cells, may lead to improvement, even inducing long-lasting remissions for patients with IMIDs. In this review, we address the unmet needs of targeted biologic therapy, delineate the critical differences between stem cell transplantation and CAR-T therapy, evaluate the current status of CAR-T therapy for IMIDs and explore its potential and existing limitations.
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Affiliation(s)
- Zhenguo Liang
- Department of Rheumatology and Immunology, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong, China
| | - Hui Xie
- Department of Clinical Research and Development, Antengene Corporation, Shanghai, China
| | - Dongze Wu
- Department of Rheumatology and Immunology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
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40
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Deng S, Xie H, Xie B. Cell-based regenerative and rejuvenation strategies for treating neurodegenerative diseases. Stem Cell Res Ther 2025; 16:167. [PMID: 40189500 PMCID: PMC11974143 DOI: 10.1186/s13287-025-04285-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Accepted: 03/19/2025] [Indexed: 04/09/2025] Open
Abstract
Neurodegenerative diseases including Alzheimer's and Parkinson's disease are age-related disorders which severely impact quality of life and impose significant societal burdens. Cellular senescence is a critical factor in these disorders, contributing to their onset and progression by promoting permanent cell cycle arrest and reducing cellular function, affecting various types of cells in brain. Recent advancements in regenerative medicine have highlighted "R3" strategies-rejuvenation, regeneration, and replacement-as promising therapeutic approaches for neurodegeneration. This review aims to critically analyze the role of cellular senescence in neurodegenerative diseases and organizes therapeutic approaches within the R3 regenerative medicine paradigm. Specifically, we examine stem cell therapy, direct lineage reprogramming, and partial reprogramming in the context of R3, emphasizing how these interventions mitigate cellular senescence and counteracting aging-related neurodegeneration. Ultimately, this review seeks to provide insights into the complex interplay between cellular senescence and neurodegeneration while highlighting the promise of cell-based regenerative strategies to address these debilitating conditions.
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Affiliation(s)
- Sixiu Deng
- Laboratory of Neurological Diseases and Brain Function, the Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
- Institute of Epigenetics and Brain Science, Southwest Medical University, Luzhou, 646000, China
- Department of Gastroenterology, The Shapingba Hospital, Chongqing University( People's Hospital of Shapingba District), Chongqing, China
| | - Huangfan Xie
- Laboratory of Neurological Diseases and Brain Function, the Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China.
- Institute of Epigenetics and Brain Science, Southwest Medical University, Luzhou, 646000, China.
| | - Bingqing Xie
- Laboratory of Neurological Diseases and Brain Function, the Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China.
- Institute of Epigenetics and Brain Science, Southwest Medical University, Luzhou, 646000, China.
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Bakr MM, Al Ankily M, Shamel M. The Protective Effects of MSC-Derived Exosomes Against Chemotherapy-Induced Parotid Gland Cytotoxicity. Int J Dent 2025; 2025:5517092. [PMID: 40223864 PMCID: PMC11986938 DOI: 10.1155/ijod/5517092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Accepted: 03/13/2025] [Indexed: 04/15/2025] Open
Abstract
Background: Fluorouracil (5-FU) is one of the most popular chemotherapeutic agents used in various cancer therapy protocols. Cell-free therapy utilizing exosomes is gaining increased popularity as a safer option due to concerns over potential tumor progression following stem cell therapy. Methods: Parotid glands of albino were treated with a single bone marrow mesenchymal stem cell (BMMSC)-derived exosomes injection (100 μg/kg/dose suspended in 0.2 mL phosphate-buffered saline [PBS]), a single 5-Fu injection (20 mg/kg), and BMMSC-derived exosomes plus 5-FU and compared to control group (daily saline injections). After 30 days, the parotid glands were examined using qualitative histological evaluation, immunohistochemical evaluation using rabbit polyclonal mouse antibody to Ki-67, caspase 3, and iNOS, as well as quantitative real-time polymerase chain reaction (RT-PCR) to evaluate gene expression of TGFβ1, TNF-α, and BCL-2. Results: Histological examination of the parotid gland revealed that BMMSC-derived exosomes restored the glands' architecture and repaired most of the distortion created by 5-FU. Immunohistochemical expression of tumor proliferation and cell death markers were restored to normal levels in the exosome-treated groups that were similar to the control group. Furthermore, BMMSC-derived exosomes reversed the effects of 5-FU on quantitative gene expression levels and showed a significant decrease in TNF-α (p < 0.001) and a significant increase in TGFβ (p < 0.0001) and BCL-2 (p < 0.05) when compared to 5-FU treatment. Conclusion: Within the limitations of the current study, BMMSC-derived exosomes have the potential to counteract the cytotoxic effects of 5-FU on the parotid glands of rats in vivo. Further studies are deemed necessary to simulate clinical scenarios.
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Affiliation(s)
- Mahmoud M. Bakr
- General Dental Practice, School of Medicine and Dentistry, Griffith University, Gold Coast, Queensland 4215, Australia
| | - Mahmoud Al Ankily
- Faculty of Dentistry, Oral Biology Department, The British University in Egypt, Cairo, Egypt
| | - Mohamed Shamel
- Faculty of Dentistry, Oral Biology Department, The British University in Egypt, Cairo, Egypt
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42
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Szeliga A, Malcher A, Niwczyk O, Olszewska M, Kurpisz M, Meczekalski B, Adashi EY. Turner syndrome: the promise of fertility via stem cell technology. Hormones (Athens) 2025:10.1007/s42000-025-00647-1. [PMID: 40169532 DOI: 10.1007/s42000-025-00647-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Accepted: 03/19/2025] [Indexed: 04/03/2025]
Abstract
Turner syndrome (TS) is the most common female sex chromosome disorder, occurring in one out of every 2500 to 3000 live female births. It is caused by the partial or complete loss of one X chromosome. TS is associated with certain physical and medical features, including short stature, estrogen deficiency, delayed puberty, hypothyroidism, and congenital heart defects. The majority of women with TS are infertile as a result of gonadal dysgenesis and primary ovarian insufficiency causing hypergonadotropic hypogonadism. Several reproductive options are available for TS patients. The recent use of stem cells (SCs) was found to constitute a promising new alternative in cases of infertility treatment in this group. SCs are undifferentiated cells that exist in embryos, fetuses, and adults and that produce differentiated cells. They can be used in infertility treatment for ovarian regeneration and oocyte generation. However, additional studies scrutinizing their efficiency and safety are needed. In our review, we present reproductive options that are currently available for women with TS.
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Affiliation(s)
- Anna Szeliga
- Department of Gynecological Endocrinology, Poznan University of Medical Sciences, Poznan, Poland
| | - Agnieszka Malcher
- Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland
| | - Olga Niwczyk
- Department of Gynecological Endocrinology, Poznan University of Medical Sciences, Poznan, Poland
| | - Marta Olszewska
- Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland
| | - Maciej Kurpisz
- Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
| | - Blazej Meczekalski
- Department of Gynecological Endocrinology, Poznan University of Medical Sciences, Poznan, Poland.
| | - Eli Y Adashi
- Department of Medical Science, Brown University, Providence, Rhode Island, USA
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43
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Forouzandegan M, Sadeghmousavi S, Heidari A, Khaboushan AS, Kajbafzadeh AM, Zolbin MM. Harnessing the potential of tissue engineering to target male infertility: Insights into testicular regeneration. Tissue Cell 2025; 93:102658. [PMID: 39689384 DOI: 10.1016/j.tice.2024.102658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 11/27/2024] [Accepted: 11/29/2024] [Indexed: 12/19/2024]
Abstract
Male infertility is among one of the most challenging health concerns in the world. Traditional therapeutic interventions such as semen and testicular tissue cryopreservation aim to restore or preserve male fertility. However, these methods are subject to limitations that impact their efficacy and are infeasible in cases such as patients who cannot produce mature sperm due to genetic or pathological disorders. Moreover, with the number of cases of prepubertal boys who must undergo gonadotoxic treatments rising, alternatives have been sought for fertility preservation to enhance reproductive rates in vitro and in vivo. Tissue engineering is a promising area that can address aspects that current therapies may not fully encompass through the creation of bioartificial testicular structures or 3D culture systems that allow the establishment of the essential conditions for sperm production. This study aims to first give a brief overview of stem cell therapy in treating male infertility and then go more in-depth regarding the novel methods and procedures based on tissue engineering that have the potential to offer new treatments for infertility caused by testicular disorders and defects.
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Affiliation(s)
- Moojan Forouzandegan
- Pediatric Urology and Regenerative Medicine Research Center, Gene Cell Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Shaghayegh Sadeghmousavi
- Pediatric Urology and Regenerative Medicine Research Center, Gene Cell Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Amirhossein Heidari
- Pediatric Urology and Regenerative Medicine Research Center, Gene Cell Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Alireza Soltani Khaboushan
- Pediatric Urology and Regenerative Medicine Research Center, Gene Cell Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Abdol-Mohammad Kajbafzadeh
- Pediatric Urology and Regenerative Medicine Research Center, Gene Cell Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
| | - Masoumeh Majidi Zolbin
- Pediatric Urology and Regenerative Medicine Research Center, Gene Cell Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
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44
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Martins F, Ribeiro MHL. Quality and Regulatory Requirements for the Manufacture of Master Cell Banks of Clinical Grade iPSCs: The EU and USA Perspectives. Stem Cell Rev Rep 2025; 21:645-679. [PMID: 39821060 DOI: 10.1007/s12015-024-10838-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/23/2024] [Indexed: 01/19/2025]
Abstract
The discovery of induced pluripotent stem cells (iPSCs) and protocols for their differentiation into various cell types have revolutionized the field of tissue engineering and regenerative medicine. Developing manufacturing guidelines for safe and GMP-compliant final products has become essential. Allogeneic iPSCs-derived cell therapies are now the preferred manufacturing alternative. This option requires the establishment of clinical-grade master cell banks of iPSCs. This study aimed at reviewing the Quality and Regulatory requirements from the two main authorities in the world-Europe (EMA) and the United States (FDA)-regarding the manufacture of clinical grade master cell banks (iPSCs). The minimum requirements for iPSCs to be used in first-in-human clinical trials were also reviewed, as well as current best practices currently followed by iPSC bank manufacturers for final product characterisation. The methodology used for this work was a review of various sources of information ranging from scientific literature, published guidance documents available on the EMA and FDA websites, GMP and ICH guidelines, and applicable compendial monographs. Manufacturers of iPSCs cell banks looking to qualify them for clinical use are turning to the ICH guidelines and trying to adapt their requirements. Specifically with the impact of the field of iPSC cell banks, the following areas should be subject to guidance and harmonisation: i) expression vectors authorized for iPSC generation; ii) minimum identity testing; iii) minimum purity testing (including adventitious agent testing); and iv) stability testing. Current ICH guidelines for biotechnological/biological products should be extended to cover cell banks used for cell therapies.
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Affiliation(s)
- Fernando Martins
- Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisboa, Portugal
- Stemamatters S.A., 4805-017, Guimarães, Portugal
| | - Maria H L Ribeiro
- Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisboa, Portugal.
- Research Institute for Medicines (i-Med.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisboa, Portugal.
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45
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Barreto-Gamarra C, Domenech M. Integrin stimulation by collagen I at the progenitor stage accelerates maturation of human iPSC-derived cardiomyocytes. J Mol Cell Cardiol 2025; 201:70-86. [PMID: 40023481 DOI: 10.1016/j.yjmcc.2025.02.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 02/12/2025] [Accepted: 02/17/2025] [Indexed: 03/04/2025]
Abstract
Cell manufacturing challenges have hampered effective preclinical evaluations of mature cardiac cells derived from human-induced pluripotent stem cells (hiPSCs). These challenges mainly stem from standard differentiation methods yielding cardiac cells of an immature phenotype, low cell yields and the need for extended culture for enhanced maturation. Although the intricate relationship between extracellular matrix (ECM) components and integrin expression levels plays a pivotal role during heart development, the impact of differentiation and maturation of cardiac cells on integrin behavior has not been thoroughly studied. This study postulates that cardiac cell maturation is significantly influenced by the timing of integrin stimulation via cell-matrix interactions. We profiled integrin expression levels throughout the differentiation process of cardiac cells and assessed the effects of utilizing defined ECM components as culture substrates on cell adhesion, proliferation, differentiation, and maturation. Our findings reveal that integrins facilitate hiPSC adhesion to ECM coated culture surfaces and underscores dynamic alterations in integrin expression during cardiac cell differentiation. Remarkably, we observed significant enrichments in α2 and β1 collagen integrin levels at the progenitor and differentiated stages. These shifts in collagen integrin levels were associated with enhanced cell seeding efficiency on collagen-type I surfaces and altered population doubling times. The stimulation of collagen integrins at the progenitor stage markedly boosted cardiac cell maturation, demonstrated by a significant (∼3-fold) increase in cardiac troponin I expression compared to the standard method after 15 days of culture. Enhanced maturation levels were further supported by significant increases in sarcomere development, maturation gene expression, morphological features, improved beating potency, and fatty acid metabolism dependency. Cardiac maturation driven by collagen was abrogated upon inhibition of collagen integrins targeted with selective pharmacological blockers, affirming their indispensable role in maturation without affecting cardiac differentiation levels. Our work confirms that stimulating collagen integrins at the progenitor stage is a potential strategy to achieve rapid maturation of hiPSC-derived cardiac cells. STATEMENT OF SIGNIFICANCE: This study offers a novel strategy guided by integrin expression levels for generating hiPSC-CMs with improved maturation features in a short culture period (<16 days). The improvements in cardiac cell maturation were achieved by stimulating collagen type 1 integrin at the progenitor stage. The potential benefits of this method for regenerative cardiac repair will pave the way for the preclinical examination of mature cardiac cells in tissues to advance cell manufacturing and cardiac toxicity studies.
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Affiliation(s)
- Carlos Barreto-Gamarra
- Department of Chemical Engineering, University of Puerto Rico-Mayagüez, Call Box 9000, Mayagüez, PR 00681-9000, United States
| | - Maribella Domenech
- Department of Chemical Engineering, University of Puerto Rico-Mayagüez, Call Box 9000, Mayagüez, PR 00681-9000, United States..
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46
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An C, Zhao Y, Guo L, Zhang Z, Yan C, Zhang S, Zhang Y, Shao F, Qi Y, wang X, Wang H, Zhang L. Innovative approaches to boost mesenchymal stem cells efficacy in myocardial infarction therapy. Mater Today Bio 2025; 31:101476. [PMID: 39896290 PMCID: PMC11787032 DOI: 10.1016/j.mtbio.2025.101476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 12/25/2024] [Accepted: 01/08/2025] [Indexed: 02/04/2025] Open
Abstract
Stem cell-based therapy has emerged as a promising approach for heart repair, potentially regenerating damaged heart tissue and improving outcomes for patients with heart disease. However, the efficacy of stem cell-based therapies remains limited by several challenges, including poor cell survival, low retention rates, poor integration, and limited functional outcomes. This article reviews current enhancement strategies to optimize mesenchymal stem cell therapy for cardiac repair. Key approaches include optimizing cell delivery methods, enhancing cell engraftment, promoting cell functions through genetic and molecular modifications, enhancing the paracrine effects of stem cells, and leveraging biomaterials and tissue engineering techniques. By focusing on these enhancement techniques, the paper highlights innovative approaches that can potentially transform stem cell therapy into a more viable and effective treatment option for cardiac repair. The ongoing research and technological advancements continue to push the boundaries, hoping to make stem cell therapy a mainstream treatment for heart disease.
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Affiliation(s)
- Chuanfeng An
- Ophthalmology and Transformational Innovation Research Center, Faculty of Medicine of Dalian University of Technology&Dalian Third People's Hospital, Dalian, 116033, PR China
- Third People's Hospital of Dalian, Dalian Eye Hospital, Dalian, 116033, PR China
| | - Yuan Zhao
- MOE Key Laboratory of Bio-Intelligent Manufacturing, Dalian Key Laboratory of Artificial Organ and Regenerative Medicine, School of Bioengineering, Dalian University of Technology, Liaoning, Dalian, 116024, PR China
| | - Lipeng Guo
- Ophthalmology and Transformational Innovation Research Center, Faculty of Medicine of Dalian University of Technology&Dalian Third People's Hospital, Dalian, 116033, PR China
- Third People's Hospital of Dalian, Dalian Eye Hospital, Dalian, 116033, PR China
| | - Zhijian Zhang
- Department of Ophthalmology, Third People's Hospital of Dalian, Dalian Medical University, Dalian, 116033, PR China
| | - Chunxiao Yan
- Department of Ophthalmology, Third People's Hospital of Dalian, Dalian Medical University, Dalian, 116033, PR China
| | - Shiying Zhang
- School of Dentistry, Shenzhen University, Shenzhen, 518060, PR China
| | - Yujie Zhang
- MOE Key Laboratory of Bio-Intelligent Manufacturing, Dalian Key Laboratory of Artificial Organ and Regenerative Medicine, School of Bioengineering, Dalian University of Technology, Liaoning, Dalian, 116024, PR China
| | - Fei Shao
- MOE Key Laboratory of Bio-Intelligent Manufacturing, Dalian Key Laboratory of Artificial Organ and Regenerative Medicine, School of Bioengineering, Dalian University of Technology, Liaoning, Dalian, 116024, PR China
| | - Yuanyuan Qi
- Ophthalmology and Transformational Innovation Research Center, Faculty of Medicine of Dalian University of Technology&Dalian Third People's Hospital, Dalian, 116033, PR China
- Third People's Hospital of Dalian, Dalian Eye Hospital, Dalian, 116033, PR China
| | - Xun wang
- Ophthalmology and Transformational Innovation Research Center, Faculty of Medicine of Dalian University of Technology&Dalian Third People's Hospital, Dalian, 116033, PR China
- Third People's Hospital of Dalian, Dalian Eye Hospital, Dalian, 116033, PR China
| | - Huanan Wang
- MOE Key Laboratory of Bio-Intelligent Manufacturing, Dalian Key Laboratory of Artificial Organ and Regenerative Medicine, School of Bioengineering, Dalian University of Technology, Liaoning, Dalian, 116024, PR China
| | - Lijun Zhang
- Ophthalmology and Transformational Innovation Research Center, Faculty of Medicine of Dalian University of Technology&Dalian Third People's Hospital, Dalian, 116033, PR China
- Third People's Hospital of Dalian, Dalian Eye Hospital, Dalian, 116033, PR China
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47
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Li W, Zhang H, Chen L, Huang C, Jiang Z, Zhou H, Zhu X, Liu X, Zheng Z, Yu Q, He Y, Gao Y, Ma J, Yang L. Cell membrane-derived nanovesicles as extracellular vesicle-mimetics in wound healing. Mater Today Bio 2025; 31:101595. [PMID: 40104636 PMCID: PMC11914519 DOI: 10.1016/j.mtbio.2025.101595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 01/28/2025] [Accepted: 02/17/2025] [Indexed: 03/20/2025] Open
Abstract
Cell membrane-derived nanovesicles (NVs) have emerged as promising alternatives to extracellular vesicles (EVs) for wound healing applications, addressing the limitations of traditional EVs, which include insufficient targeting capability, low production yield, and limited drug-loading capacity. Through mechanical cell extrusion methods, NVs exhibit superior characteristics, demonstrating enhanced yield, stability, and purity compared to natural EVs. These NVs can be derived from various membrane sources, including single cell types (stem cells, blood cells, immune cells, and bacterial membranes), hybrid cell membranes and cell membranes mixed with liposomes, with each offering unique therapeutic properties. The integration of genetic engineering and surface modifications has further enhanced NV functionality, enabling precise targeting and improved drug delivery capabilities. Recent advances in NV-based therapies have demonstrated their potential across multiple biomedical applications. Although challenges persist in terms of standardization, storage stability, and clinical translation, the combination of natural cell-derived functions with artificial modification potential positions NVs as a promising platform for next-generation therapeutic delivery systems, thereby offering new possibilities in wound healing applications. Finally, we explore the challenges and future prospects of translating NV-based therapeutics into clinical practice, providing insights into the future development of this innovative approach in wound healing and tissue repair.
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Affiliation(s)
- Wenwen Li
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Huihui Zhang
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Lianglong Chen
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Chaoyang Huang
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Ziwei Jiang
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Hai Zhou
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Xinxi Zhu
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Xiaoyang Liu
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Zesen Zheng
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Qiuyi Yu
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Yufang He
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Yanbin Gao
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Jun Ma
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Lei Yang
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
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48
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Li L, Liu Y, Wang K, Mo J, Weng Z, Jiang H, Jin C. Stem cell exosomes: new hope and future potential for relieving liver fibrosis. Clin Mol Hepatol 2025; 31:333-349. [PMID: 39510097 PMCID: PMC12016649 DOI: 10.3350/cmh.2024.0854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 10/30/2024] [Accepted: 11/05/2024] [Indexed: 11/15/2024] Open
Abstract
Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.
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Affiliation(s)
- Lihua Li
- 1 Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, Zhejiang Province, P. R. China
| | - Yongjie Liu
- Department of Cell biology, School of Medicine, Taizhou University, Taizhou, Zhejiang Province, P. R. China
- Department of Pathophysiology, School of Basic Medicine, Shenyang Medical College, Shenyang, Liaoning Province, P. R. China
| | - Kunpeng Wang
- 1 Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, Zhejiang Province, P. R. China
| | - Jinggang Mo
- 1 Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, Zhejiang Province, P. R. China
| | - Zhiyong Weng
- 1 Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, Zhejiang Province, P. R. China
| | - Hao Jiang
- 1 Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, Zhejiang Province, P. R. China
| | - Chong Jin
- 1 Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, Zhejiang Province, P. R. China
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49
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Shiina T, Kimura K, Takemoto Y, Tanaka K, Kato R. Importance of dataset design in developing robust U-Net models for label-free cell morphology evaluation. J Biosci Bioeng 2025; 139:329-339. [PMID: 39933975 DOI: 10.1016/j.jbiosc.2025.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Revised: 01/10/2025] [Accepted: 01/19/2025] [Indexed: 02/13/2025]
Abstract
Advances in regenerative medicine highlighted the need for label-free cell image analysis to replace conventional microscopic observation for non-invasive cell quality evaluation. Image-based evaluation provides an efficient, quantitative, and automated approach to cell analysis, but segmentation remains a critical and challenging step. In this study, we investigated how training dataset design influenced the robustness of U-Net models for cell segmentation, focusing on challenges posed by limited data availability in cell culture. Using 2592 image pairs from four cell types representing key morphological categories, we constructed 42 investigation patterns to evaluate the effects of dataset size, dataset content, and morphological diversity on model performance. Our results showed that robust segmentation models could be developed with approximately 10 raw images captured using a 4× objective lens, a much smaller dataset than typically assumed. The dataset content was found to be crucial: training dataset images that captured commonly observed cell patterns yielded more robust models compared to those capturing rare or irregular cell patterns, which often impaired model performance with large deviations. Additionally, including both spindle and round cell morphologies in the training datasets improved model robustness when tested across all four cell types, while datasets restricted to a single morphology type could not achieve robust models. These findings highlight the importance of curating datasets that capture representative yet diverse cell morphologies. By addressing critical questions about dataset design, this study provides actionable guidance for the effective use of deep learning-based cell segmentation models in manufacturing and research applications.
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Affiliation(s)
- Takeru Shiina
- Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Tokai National Higher Education and Research System, Furocho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan
| | - Kazue Kimura
- Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Tokai National Higher Education and Research System, Furocho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan
| | - Yuto Takemoto
- Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Tokai National Higher Education and Research System, Furocho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan
| | - Kenjiro Tanaka
- Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Tokai National Higher Education and Research System, Furocho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan
| | - Ryuji Kato
- Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Tokai National Higher Education and Research System, Furocho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan; Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Tokai National Higher Education and Research System, Furocho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan.
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50
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Felix RB, Shabazz A, Holeman WP, Han S, Wyble M, Uzoukwu M, Gomes LA, Nho L, Litman MZ, Hu P, Fisher JP. From Promise to Practice: Recent Growth in 30 Years of Tissue Engineering Commercialization. Tissue Eng Part A 2025; 31:285-302. [PMID: 38818800 DOI: 10.1089/ten.tea.2024.0112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/01/2024] Open
Abstract
This perspective, marking the 30th anniversary of the Tissue Engineering journal, discusses the exciting trends in the global commercialization of tissue engineering technology. Within a historical context, we present an evolution of challenges and a discussion of the last 5 years of global commercial successes and emerging market trends, highlighting the continued expansion of the field in the northeastern United States. This leads to an overview of the last 5 years' progress in clinical trials for tissue-engineered therapeutics, including an analysis of trends in success and failure. Finally, we provide a broad overview of preclinical research and a perspective on where the state-of-the-art lies on the horizon.
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Affiliation(s)
- Ryan B Felix
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA
- Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Amal Shabazz
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA
| | - William Pieper Holeman
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA
| | - Sarang Han
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA
| | - Matthew Wyble
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA
| | - Marylyn Uzoukwu
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA
| | - Lauren Audrey Gomes
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA
| | - Laena Nho
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA
| | - Mark Zachary Litman
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA
| | - Peter Hu
- Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - John P Fisher
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, Maryland, USA
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