|
1
|
Dhillon J, Maguire JA, Kraeutler MJ. Stromal cell-based injection therapies for the treatment of knee osteoarthritis: A systematic review of level I randomized controlled trials. OSTEOARTHRITIS AND CARTILAGE OPEN 2025; 7:100608. [PMID: 40290651 PMCID: PMC12033899 DOI: 10.1016/j.ocarto.2025.100608] [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: 04/02/2024] [Accepted: 03/27/2025] [Indexed: 04/30/2025] Open
Abstract
Objective To systematically review randomized controlled trials (RCTs) to compare clinical outcomes of stromal cell-based injection therapies versus other non-operative treatment modalities for the treatment of knee osteoarthritis (OA). Method A systematic review was performed by searching PubMed, Cochrane Library, and EMBASE to locate RCTs, published since 2019, comparing stromal cell-based injection therapies versus other non-operative modalities for the treatment of knee OA. The search terms used were: knee AND osteoarthritis AND injection AND randomized. Results Seventeen studies (all Level I evidence) were included in this review with 972 patients undergoing treatment with stromal cell-based therapy (Intervention Group) and 651 patients in the control group (Control Group). Among the 17 studies, 7 used autologous adipose-derived mesenchymal stromal cells (MSCs) (ADMSCs), 2 studies used allogeneic ADMSCs, 4 used autologous bone marrow-derived MSCs (BMMSCs), 1 used allogeneic BMMSCs, 1 used allogeneic placental MSCs, 1 used umbilical cord-derived MSCs (UCMSCs), and 1 study used autologous ADMSCs, BMMSCs, or allogeneic UCMSCs. All but 3 studies reported significantly better clinical or radiological outcomes in the Intervention Group at final follow-up. A total of 5 and 3 studies reported adverse events occurring in the Intervention and the Control groups, respectively, but they were all self-limiting. Conclusions Patients undergoing treatment of knee OA with MSCs might be expected to experience improvements in clinical and radiological outcomes in comparison to other non-operative modalities. Additional studies with mid-to long-term outcomes are needed to better determine the efficacy and safety of MSCs for the treatment of knee OA.
Collapse
Affiliation(s)
- Jaydeep Dhillon
- Samaritan Health Services, Department of Orthopedics, Corvallis, OR 97330, USA
| | - James A. Maguire
- St. Joseph's University Medical Center, Department of Orthopaedic Surgery, Paterson, NJ 07503, USA
| | - Matthew J. Kraeutler
- Texas Tech University Health Sciences Center, Department of Orthopaedic Surgery & Rehabilitation, Lubbock, TX 79430, USA
| |
Collapse
|
|
2
|
Hua Z, Zhao Y, Zhang M, Wang Y, Feng H, Wei X, Wu X, Chen W, Xue Y. Research progress on intervertebral disc repair strategies and mechanisms based on hydrogel. J Biomater Appl 2025; 39:1121-1142. [PMID: 39929142 DOI: 10.1177/08853282251320227] [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: 04/03/2025]
Abstract
Intervertebral disc degeneration (IDD) arises from a complex interplay of genetic, environmental, and age-related factors, culminating in a spectrum of low back pain (LBP) disorders that exert significant societal and economic impact. The present therapeutic landscape for IDD poses formidable clinical hurdles, necessitating the exploration of innovative treatment modalities. The hydrogel, as a biomaterial, exhibits superior biocompatibility compared to other biomaterials such as bioceramics and bio-metal materials. It also demonstrates mechanical properties closer to those of natural intervertebral discs (IVDs) and favorable biodegradability conducive to IVD regeneration. Therefore, it has emerged as a promising candidate material in the field of regenerative medicine and tissue engineering for treating IDD. Hydrogels have made significant strides in the field of IDD treatment. Particularly, injectable hydrogels not only provide mechanical support but also enable controlled release of bioactive molecules, playing a crucial role in mitigating inflammation and promoting extracellular matrix (ECM) regeneration. Furthermore, the ability of injectable hydrogels to achieve minimally invasive implantation helps minimize tissue damage. This article initially provides a concise exposition of the structure and function of IVD, the progression of IDD, and delineates extant clinical interventions for IDD. Subsequently, it categorizes hydrogels, encapsulates recent advancements in biomaterials and cellular therapies, and delves into the mechanisms through which hydrogels foster disc regeneration. Ultimately, the article deliberates on the prospects and challenges attendant to hydrogel therapy for IDD.
Collapse
Affiliation(s)
- Zekun Hua
- College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan, China
| | - Yinuo Zhao
- College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan, China
| | - Meng Zhang
- College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan, China
| | - Yanqin Wang
- College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan, China
| | - Haoyu Feng
- Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
| | - Xiaochun Wei
- Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Xiaogang Wu
- College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan, China
- Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Weiyi Chen
- College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan, China
| | - Yanru Xue
- College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan, China
- Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
| |
Collapse
|
|
3
|
Liu L, Chen S, Song Y, Cui L, Chen Y, Xia J, Fan Y, Yang L, Yang L. Hydrogels empowered mesenchymal stem cells and the derived exosomes for regenerative medicine in age-related musculoskeletal diseases. Pharmacol Res 2025; 213:107618. [PMID: 39892438 DOI: 10.1016/j.phrs.2025.107618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Revised: 01/09/2025] [Accepted: 01/17/2025] [Indexed: 02/03/2025]
Abstract
As the population ages, musculoskeletal diseases (MSK) have emerged as a significant burden for individuals, healthcare systems, and social care systems. Recently, regenerative medicine has exhibited vast potential in age-related MSK, with mesenchymal stromal cells (MSCs) and their derived exosomes (Exos) therapies showing distinct advantages. However, these therapies face several limitations, including issues related to ensuring stability and effective distribution within the body. Hydrogels, acting as an ideal carrier, can enhance the therapeutic effects and application range of MSCs and Exos derived from MSCs (MSC-Exos). Therefore, this review comprehensively summarizes the application progress of MSCs and MSC-Exos combined with hydrogels in age-related MSK disease research. It aims to provide a detailed perspective, showcasing the functional enhancement of MSCs and MSC-Exos when incorporated into hydrogels. Additionally, this review explores their potential and challenges in treating age-related MSK diseases, offering references for future research directions and potential innovative strategies.
Collapse
Affiliation(s)
- Lixin Liu
- Departments of Geriatrics, The First Hospital of China Medical University, Shenyang, Liaoning 110001, PR China
| | - Siwen Chen
- Research Center for Biomedical Materials, Shenyang Key Laboratory of Biomedical Polymers, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang 110004, PR China; Center for Molecular Science and Engineering, College of Science, Northeastern University, Shenyang 110819, PR China
| | - Yantao Song
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110002, PR China
| | - Longwei Cui
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110002, PR China
| | - Yiman Chen
- Departments of Geriatrics, The First Hospital of China Medical University, Shenyang, Liaoning 110001, PR China
| | - Jiangli Xia
- School of Pharmaceutical Science, Liaoning University, Shenyang 110036, PR China
| | - Yibo Fan
- Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Liqun Yang
- Research Center for Biomedical Materials, Shenyang Key Laboratory of Biomedical Polymers, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang 110004, PR China.
| | - Lina Yang
- Departments of Geriatrics, The First Hospital of China Medical University, Shenyang, Liaoning 110001, PR China; Department of International Physical Examination Center, The First Hospital of China Medical University, Shenyang, Liaoning 110001, PR China.
| |
Collapse
|
|
4
|
Ruan MF, Yin YH, Shao XD, Qi XS. Bone marrow mesenchymal stem cell transplantation for treatment of liver cirrhosis: Recent advances. Shijie Huaren Xiaohua Zazhi 2025; 33:106-113. [DOI: 10.11569/wcjd.v33.i2.106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 01/20/2025] [Accepted: 02/20/2025] [Indexed: 02/28/2025] Open
Affiliation(s)
- Meng-Fan Ruan
- Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of Jinzhou Medical University), Shenyang 110840, Liaoning Province, China
- Postgraduate College, Jinzhou Medical University, Jinzhou 121001, Liaoning Province, China
| | - Yu-Hang Yin
- Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of Jinzhou Medical University), Shenyang 110840, Liaoning Province, China
- Postgraduate College, China Medical University, Shenyang 110122, Liaoning Province, China
| | - Xiao-Dong Shao
- Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of Jinzhou Medical University), Shenyang 110840, Liaoning Province, China
| | - Xing-Shun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of Jinzhou Medical University), Shenyang 110840, Liaoning Province, China
- Postgraduate College, Jinzhou Medical University, Jinzhou 121001, Liaoning Province, China
- Postgraduate College, China Medical University, Shenyang 110122, Liaoning Province, China
| |
Collapse
|
|
5
|
Wu KY, Osman R, Kearn N, Kalevar A. Three-Dimensional Bioprinting for Retinal Tissue Engineering. Biomimetics (Basel) 2024; 9:733. [PMID: 39727737 DOI: 10.3390/biomimetics9120733] [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: 11/01/2024] [Revised: 11/20/2024] [Accepted: 11/25/2024] [Indexed: 12/28/2024] Open
Abstract
Three-dimensional bioprinting (3DP) is transforming the field of regenerative medicine by enabling the precise fabrication of complex tissues, including the retina, a highly specialized and anatomically complex tissue. This review provides an overview of 3DP's principles, its multi-step process, and various bioprinting techniques, such as extrusion-, droplet-, and laser-based methods. Within the scope of biomimicry and biomimetics, emphasis is placed on how 3DP potentially enables the recreation of the retina's natural cellular environment, structural complexity, and biomechanical properties. Focusing on retinal tissue engineering, we discuss the unique challenges posed by the retina's layered structure, vascularization needs, and the complex interplay between its numerous cell types. Emphasis is placed on recent advancements in bioink formulations, designed to emulate retinal characteristics and improve cell viability, printability, and mechanical stability. In-depth analyses of bioinks, scaffold materials, and emerging technologies, such as microfluidics and organ-on-a-chip, highlight the potential of bioprinted models to replicate retinal disease states, facilitating drug development and testing. While challenges remain in achieving clinical translation-particularly in immune compatibility and long-term integration-continued innovations in bioinks and scaffolding are paving the way toward functional retinal constructs. We conclude with insights into future research directions, aiming to refine 3DP for personalized therapies and transformative applications in vision restoration.
Collapse
Affiliation(s)
- Kevin Y Wu
- Department of Surgery, Division of Ophthalmology, University of Sherbrooke, Sherbrooke, QC J1G 2E8, Canada
| | - Rahma Osman
- Department of Medicine, School of Medicine, Queen's University, Kingston, ON K7L 3N6, Canada
| | - Natalie Kearn
- Department of Medicine, School of Medicine, Queen's University, Kingston, ON K7L 3N6, Canada
| | - Ananda Kalevar
- Department of Surgery, Division of Ophthalmology, University of Sherbrooke, Sherbrooke, QC J1G 2E8, Canada
| |
Collapse
|
|
6
|
Zhang M, Ye Q, Zhu Z, Shi S, Xu C, Xie R, Li Y. Hyaluronic Acid-Based Dynamic Hydrogels for Cartilage Repair and Regeneration. Gels 2024; 10:703. [PMID: 39590059 PMCID: PMC11594165 DOI: 10.3390/gels10110703] [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] [Received: 09/30/2024] [Revised: 10/27/2024] [Accepted: 10/29/2024] [Indexed: 11/28/2024] Open
Abstract
Hyaluronic acid (HA), an important natural polysaccharide and meanwhile, an essential component of extracellular matrix (ECM), has been widely used in tissue repair and regeneration due to its high biocompatibility, biodegradation, and bioactivity, and the versatile chemical groups for modification. Specially, HA-based dynamic hydrogels, compared with the conventional hydrogels, offer an adaptable network and biomimetic microenvironment to optimize tissue repair and the regeneration process with a striking resemblance to ECM. Herein, this review comprehensively summarizes the recent advances of HA-based dynamic hydrogels and focuses on their applications in articular cartilage repair. First, the fabrication methods and advantages of HA dynamic hydrogels are presented. Then, the applications of HA dynamic hydrogels in cartilage repair are illustrated from the perspective of cell-free and cell-encapsulated and/or bioactive molecules (drugs, factors, and ions). Finally, the current challenges and prospective directions are outlined.
Collapse
Affiliation(s)
- Mingshuo Zhang
- School of Medical Information Engineering, Gannan Medical University, Ganzhou 341000, China; (M.Z.); (Q.Y.); (Z.Z.); (S.S.)
- Jiangxi Provincial Key Laboratory of Tissue Engineering (2024SSY06291), Gannan Medical University, Ganzhou 341000, China;
| | - Qianwen Ye
- School of Medical Information Engineering, Gannan Medical University, Ganzhou 341000, China; (M.Z.); (Q.Y.); (Z.Z.); (S.S.)
- Jiangxi Provincial Key Laboratory of Tissue Engineering (2024SSY06291), Gannan Medical University, Ganzhou 341000, China;
| | - Zebo Zhu
- School of Medical Information Engineering, Gannan Medical University, Ganzhou 341000, China; (M.Z.); (Q.Y.); (Z.Z.); (S.S.)
- Jiangxi Provincial Key Laboratory of Tissue Engineering (2024SSY06291), Gannan Medical University, Ganzhou 341000, China;
| | - Shuanglian Shi
- School of Medical Information Engineering, Gannan Medical University, Ganzhou 341000, China; (M.Z.); (Q.Y.); (Z.Z.); (S.S.)
- Jiangxi Provincial Key Laboratory of Tissue Engineering (2024SSY06291), Gannan Medical University, Ganzhou 341000, China;
| | - Chunming Xu
- Jiangxi Provincial Key Laboratory of Tissue Engineering (2024SSY06291), Gannan Medical University, Ganzhou 341000, China;
- School of Basic Medicine, Gannan Medical University, Ganzhou 341000, China
| | - Renjian Xie
- School of Medical Information Engineering, Gannan Medical University, Ganzhou 341000, China; (M.Z.); (Q.Y.); (Z.Z.); (S.S.)
- Jiangxi Provincial Key Laboratory of Tissue Engineering (2024SSY06291), Gannan Medical University, Ganzhou 341000, China;
- Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases (Ministry of Education), Gannan Medical University, Ganzhou 341000, China
| | - Yumei Li
- Jiangxi Provincial Key Laboratory of Tissue Engineering (2024SSY06291), Gannan Medical University, Ganzhou 341000, China;
- School of Basic Medicine, Gannan Medical University, Ganzhou 341000, China
| |
Collapse
|
|
7
|
Cui X, Jiao J, Yang L, Wang Y, Jiang W, Yu T, Li M, Zhang H, Chao B, Wang Z, Wu M. Advanced tumor organoid bioprinting strategy for oncology research. Mater Today Bio 2024; 28:101198. [PMID: 39205873 PMCID: PMC11357813 DOI: 10.1016/j.mtbio.2024.101198] [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: 04/10/2024] [Revised: 07/14/2024] [Accepted: 08/08/2024] [Indexed: 09/04/2024] Open
Abstract
Bioprinting is a groundbreaking technology that enables precise distribution of cell-containing bioinks to construct organoid models that accurately reflect the characteristics of tumors in vivo. By incorporating different types of tumor cells into the bioink, the heterogeneity of tumors can be replicated, enabling studies to simulate real-life situations closely. Precise reproduction of the arrangement and interactions of tumor cells using bioprinting methods provides a more realistic representation of the tumor microenvironment. By mimicking the complexity of the tumor microenvironment, the growth patterns and diffusion of tumors can be demonstrated. This approach can also be used to evaluate the response of tumors to drugs, including drug permeability and cytotoxicity, and other characteristics. Therefore, organoid models can provide a more accurate oncology research and treatment simulation platform. This review summarizes the latest advancements in bioprinting to construct tumor organoid models. First, we describe the bioink used for tumor organoid model construction, followed by an introduction to various bioprinting methods for tumor model formation. Subsequently, we provide an overview of existing bioprinted tumor organoid models.
Collapse
Affiliation(s)
- Xiangran Cui
- Department of Orthopedics, The Second Hospital of Jilin University Changchun, 130041, PR China
| | - Jianhang Jiao
- Department of Orthopedics, The Second Hospital of Jilin University Changchun, 130041, PR China
| | - Lili Yang
- Department of Orthopedics, The Second Hospital of Jilin University Changchun, 130041, PR China
| | - Yang Wang
- Department of Orthopedics, The Second Hospital of Jilin University Changchun, 130041, PR China
| | - Weibo Jiang
- Department of Orthopedics, The Second Hospital of Jilin University Changchun, 130041, PR China
| | - Tong Yu
- Department of Orthopedics, The Second Hospital of Jilin University Changchun, 130041, PR China
| | - Mufeng Li
- Department of Orthopedics, The Second Hospital of Jilin University Changchun, 130041, PR China
| | - Han Zhang
- Department of Orthopedics, The Second Hospital of Jilin University Changchun, 130041, PR China
| | - Bo Chao
- Department of Orthopedics, The Second Hospital of Jilin University Changchun, 130041, PR China
| | - Zhonghan Wang
- Department of Orthopedics, The Second Hospital of Jilin University Changchun, 130041, PR China
- Orthopaedic Research Institute of Jilin Province, Changchun, 130041, PR China
| | - Minfei Wu
- Department of Orthopedics, The Second Hospital of Jilin University Changchun, 130041, PR China
| |
Collapse
|
|
8
|
Shu Y, Li B, Ma H, Liu J, Cheng YY, Li X, Liu T, Yang C, Ma X, Song K. Three-dimensional breast cancer tumor models based on natural hydrogels: a review. J Zhejiang Univ Sci B 2024; 25:736-755. [PMID: 39308065 PMCID: PMC11422793 DOI: 10.1631/jzus.b2300840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/27/2024]
Abstract
Breast cancer is the most common cancer in women and one of the deadliest cancers worldwide. According to the distribution of tumor tissue, breast cancer can be divided into invasive and non-invasive forms. The cancer cells in invasive breast cancer pass through the breast and through the immune system or systemic circulation to different parts of the body, forming metastatic breast cancer. Drug resistance and distant metastasis are the main causes of death from breast cancer. Research on breast cancer has attracted extensive attention from researchers. In vitro construction of tumor models by tissue engineering methods is a common tool for studying cancer mechanisms and anticancer drug screening. The tumor microenvironment consists of cancer cells and various types of stromal cells, including fibroblasts, endothelial cells, mesenchymal cells, and immune cells embedded in the extracellular matrix. The extracellular matrix contains fibrin proteins (such as types I, II, III, IV, VI, and X collagen and elastin) and glycoproteins (such as proteoglycan, laminin, and fibronectin), which are involved in cell signaling and binding of growth factors. The current traditional two-dimensional (2D) tumor models are limited by the growth environment and often cannot accurately reproduce the heterogeneity and complexity of tumor tissues in vivo. Therefore, in recent years, research on three-dimensional (3D) tumor models has gradually increased, especially 3D bioprinting models with high precision and repeatability. Compared with a 2D model, the 3D environment can better simulate the complex extracellular matrix components and structures in the tumor microenvironment. Three-dimensional models are often used as a bridge between 2D cellular level experiments and animal experiments. Acellular matrix, gelatin, sodium alginate, and other natural materials are widely used in the construction of tumor models because of their excellent biocompatibility and non-immune rejection. Here, we review various natural scaffold materials and construction methods involved in 3D tissue-engineered tumor models, as a reference for research in the field of breast cancer.
Collapse
Affiliation(s)
- Yan Shu
- State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China
| | - Bing Li
- State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China
| | - Hailin Ma
- State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China
| | - Jiaqi Liu
- State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China
| | - Yuen Yee Cheng
- Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney, NSW 2007, Australia
| | - Xiangqin Li
- State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China
| | - Tianqing Liu
- State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China
| | - Chuwei Yang
- Emergency Center, the Second Hospital of Dalian Medical University, Dalian 116023, China. ,
| | - Xiao Ma
- Department of Anesthesia, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China. ,
| | - Kedong Song
- State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China.
| |
Collapse
|
|
9
|
Pozo-Pérez L, Tornero-Esteban P, López-Bran E. Clinical and preclinical approach in AGA treatment: a review of current and new therapies in the regenerative field. Stem Cell Res Ther 2024; 15:260. [PMID: 39148125 PMCID: PMC11328498 DOI: 10.1186/s13287-024-03801-5] [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: 04/26/2024] [Accepted: 06/11/2024] [Indexed: 08/17/2024] Open
Abstract
Androgenetic alopecia (AGA) is the most prevalent type of hair loss. Its morbility is mainly psychological although an increased incidence in melanoma has also been observed in affected subjects. Current drug based therapies and physical treatments are either unsuccessful in the long term or have relevant side effects that limit their application. Therefore, a new therapeutic approach is needed to promote regenerative enhancement alternatives. These treatment options, focused on the cellular niche restoration, could be the solution to the impact of dihydrotestosterone in the hair follicle microenvironment. In this context emerging regenerative therapies such as Platelet-rich plasma or Platelet-rich fibrine as well as hair follicle stem cells and mesenchymal stem cell based therapies and their derivatives (conditioned medium CM or exoxomes) are highlighting in the evolving landscape of hair restoration. Nanotechnology is also leading the way in AGA treatment through the design of bioinks and nanobiomaterials whose structures are being configuring in a huge range of cases by means of 3D bioprinting. Due to the increasing number and the rapid creation of new advanced therapies alternatives in the AGA field, an extended review of the current state of art is needed. In addition this review provides a general insight in current and emerging AGA therapies which is intented to be a guidance for researchers highlighting the cutting edge treatments which are recently gaining ground.
Collapse
Affiliation(s)
- Lorena Pozo-Pérez
- Dermatology Department, Clínico San Carlos Hospital, Madrid, Spain.
- Institute for Health Research of Clinico San Carlos Hospital (IdISSC), Madrid, Spain.
| | - Pilar Tornero-Esteban
- Cellular GMP Manufacturing Facility, Institute for Health Research of Clinico San Carlos Hospital (IdISSC), Madrid, Spain
| | | |
Collapse
|
|
10
|
Wei Q, An Y, Zhao X, Li M, Zhang J. Three-dimensional bioprinting of tissue-engineered skin: Biomaterials, fabrication techniques, challenging difficulties, and future directions: A review. Int J Biol Macromol 2024; 266:131281. [PMID: 38641503 DOI: 10.1016/j.ijbiomac.2024.131281] [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: 12/31/2023] [Revised: 03/17/2024] [Accepted: 03/29/2024] [Indexed: 04/21/2024]
Abstract
As an emerging new manufacturing technology, Three-dimensional (3D) bioprinting provides the potential for the biomimetic construction of multifaceted and intricate architectures of functional integument, particularly functional biomimetic dermal structures inclusive of cutaneous appendages. Although the tissue-engineered skin with complete biological activity and physiological functions is still cannot be manufactured, it is believed that with the advances in matrix materials, molding process, and biotechnology, a new generation of physiologically active skin will be born in the future. In pursuit of furnishing readers and researchers involved in relevant research to have a systematic and comprehensive understanding of 3D printed tissue-engineered skin, this paper furnishes an exegesis on the prevailing research landscape, formidable obstacles, and forthcoming trajectories within the sphere of tissue-engineered skin, including: (1) the prevalent biomaterials (collagen, chitosan, agarose, alginate, etc.) routinely employed in tissue-engineered skin, and a discerning analysis and comparison of their respective merits, demerits, and inherent characteristics; (2) the underlying principles and distinguishing attributes of various current printing methodologies utilized in tissue-engineered skin fabrication; (3) the present research status and progression in the realm of tissue-engineered biomimetic skin; (4) meticulous scrutiny and summation of the extant research underpinning tissue-engineered skin inform the identification of prevailing challenges and issues.
Collapse
Affiliation(s)
- Qinghua Wei
- School of Mechanical Engineering, Northwestern Polytechnical University, Xi'an 710072, China; Innovation Center NPU Chongqing, Northwestern Polytechnical University, Chongqing 400000, China.
| | - Yalong An
- School of Mechanical Engineering, Northwestern Polytechnical University, Xi'an 710072, China
| | - Xudong Zhao
- School of Mechanical Engineering, Northwestern Polytechnical University, Xi'an 710072, China
| | - Mingyang Li
- School of Mechanical Engineering, Northwestern Polytechnical University, Xi'an 710072, China
| | - Juan Zhang
- School of Mechanical Engineering, Northwestern Polytechnical University, Xi'an 710072, China
| |
Collapse
|
|
11
|
Zhang X, Yang Z, Zhang D, Bai M. The role of Semaphorin 3A in oral diseases. Oral Dis 2024; 30:1887-1896. [PMID: 37771213 DOI: 10.1111/odi.14748] [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: 04/12/2023] [Revised: 09/11/2023] [Accepted: 09/13/2023] [Indexed: 09/30/2023]
Abstract
Semaphorin 3A (SEMA3A), also referred to as H-Sema III, is a molecule with significant biological importance in regulating physiological and pathological processes. However, its role in oral diseases, particularly its association with inflammatory immunity and alveolar bone remodeling defects, remains poorly understood. This comprehensive review article aims to elucidate the recent advances in understanding SEMA3A in the oral system, encompassing nerve formation, periodontitis, pulpitis, apical periodontitis, and oral squamous cell carcinoma. Notably, we explore its novel function in inflammatory immunomodulation and alveolar bone formation during oral infectious diseases. By doing so, this review enhances our comprehension of SEMA3A's role in oral biology and opens up possibilities for modulatory approaches and potential treatments in oral diseases.
Collapse
Affiliation(s)
- Xinyue Zhang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Zhenqi Yang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Demao Zhang
- Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China
| | - Mingru Bai
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| |
Collapse
|
|
12
|
Chen Y, Luo X, Kang R, Cui K, Ou J, Zhang X, Liang P. Current therapies for osteoarthritis and prospects of CRISPR-based genome, epigenome, and RNA editing in osteoarthritis treatment. J Genet Genomics 2024; 51:159-183. [PMID: 37516348 DOI: 10.1016/j.jgg.2023.07.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 07/13/2023] [Accepted: 07/15/2023] [Indexed: 07/31/2023]
Abstract
Osteoarthritis (OA) is one of the most common degenerative joint diseases worldwide, causing pain, disability, and decreased quality of life. The balance between regeneration and inflammation-induced degradation results in multiple etiologies and complex pathogenesis of OA. Currently, there is a lack of effective therapeutic strategies for OA treatment. With the development of CRISPR-based genome, epigenome, and RNA editing tools, OA treatment has been improved by targeting genetic risk factors, activating chondrogenic elements, and modulating inflammatory regulators. Supported by cell therapy and in vivo delivery vectors, genome, epigenome, and RNA editing tools may provide a promising approach for personalized OA therapy. This review summarizes CRISPR-based genome, epigenome, and RNA editing tools that can be applied to the treatment of OA and provides insights into the development of CRISPR-based therapeutics for OA treatment. Moreover, in-depth evaluations of the efficacy and safety of these tools in human OA treatment are needed.
Collapse
Affiliation(s)
- Yuxi Chen
- MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510275, China
| | - Xiao Luo
- MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510275, China
| | - Rui Kang
- MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510275, China
| | - Kaixin Cui
- MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510275, China
| | - Jianping Ou
- Center for Reproductive Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong 510630, China
| | - Xiya Zhang
- Center for Reproductive Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
| | - Puping Liang
- MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510275, China.
| |
Collapse
|
|
13
|
Lee G, Han SB, Kim SH, Jeong S, Kim DH. Stretching of porous poly (l-lactide-co-ε-caprolactone) membranes regulates the differentiation of mesenchymal stem cells. Front Cell Dev Biol 2024; 12:1303688. [PMID: 38333594 PMCID: PMC10850303 DOI: 10.3389/fcell.2024.1303688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 01/12/2024] [Indexed: 02/10/2024] Open
Abstract
Background: Among a variety of biomaterials supporting cell growth for therapeutic applications, poly (l-lactide-co-ε-caprolactone) (PLCL) has been considered as one of the most attractive scaffolds for tissue engineering owing to its superior mechanical strength, biocompatibility, and processibility. Although extensive studies have been conducted on the relationship between the microstructure of polymeric materials and their mechanical properties, the use of the fine-tuned morphology and mechanical strength of PLCL membranes in stem cell differentiation has not yet been studied. Methods: PLCL membranes were crystallized in a combination of diverse solvent-nonsolvent mixtures, including methanol (MeOH), isopropanol (IPA), chloroform (CF), and distilled water (DW), with different solvent polarities. A PLCL membrane with high mechanical strength induced by limited pore formation was placed in a custom bioreactor mimicking the reproducible physiological microenvironment of the vascular system to promote the differentiation of mesenchymal stem cells (MSCs) into smooth muscle cells (SMCs). Results: We developed a simple, cost-effective method for fabricating porosity-controlled PLCL membranes based on the crystallization of copolymer chains in a combination of solvents and non-solvents. We confirmed that an increase in the ratio of the non-solvent increased the chain aggregation of PLCL by slow evaporation, leading to improved mechanical properties of the PLCL membrane. Furthermore, we demonstrated that the cyclic stretching of PLCL membranes induced MSC differentiation into SMCs within 10 days of culture. Conclusion: The combination of solvent and non-solvent casting for PLCL solidification can be used to fabricate mechanically durable polymer membranes for use as mechanosensitive scaffolds for stem cell differentiation.
Collapse
Affiliation(s)
- Geonhui Lee
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, United States
- Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, United States
| | - Seong-Beom Han
- KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea
| | - Soo Hyun Kim
- KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea
- Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology, Seoul, Republic of Korea
| | - Sangmoo Jeong
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, United States
- Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, United States
| | - Dong-Hwee Kim
- KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea
- Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology, Seoul, Republic of Korea
- Department of Integrative Energy Engineering, College of Engineering, Korea University, Seoul, Republic of Korea
| |
Collapse
|
|
14
|
He W, Deng J, Ma B, Tao K, Zhang Z, Ramakrishna S, Yuan W, Ye T. Recent Advancements of Bioinks for 3D Bioprinting of Human Tissues and Organs. ACS APPLIED BIO MATERIALS 2024; 7:17-43. [PMID: 38091514 DOI: 10.1021/acsabm.3c00806] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2024]
Abstract
3D bioprinting is recognized as a promising biomanufacturing technology that enables the reproducible and high-throughput production of tissues and organs through the deposition of different bioinks. Especially, bioinks based on loaded cells allow for immediate cellularity upon printing, providing opportunities for enhanced cell differentiation for organ manufacturing and regeneration. Thus, extensive applications have been found in the field of tissue engineering. The performance of the bioinks determines the functionality of the entire printed construct throughout the bioprinting process. It is generally expected that bioinks should support the encapsulated cells to achieve their respective cellular functions and withstand normal physiological pressure exerted on the printed constructs. The bioinks should also exhibit a suitable printability for precise deposition of the constructs. These characteristics are essential for the functional development of tissues and organs in bioprinting and are often achieved through the combination of different biomaterials. In this review, we have discussed the cutting-edge outstanding performance of different bioinks for printing various human tissues and organs in recent years. We have also examined the current status of 3D bioprinting and discussed its future prospects in relieving or curing human health problems.
Collapse
Affiliation(s)
- Wen He
- Ministry of Education Key Laboratory of Micro/Nano Systems for Aerospace, Northwestern Polytechnical University, Xi'an 710072, China
| | - Jinjun Deng
- Ministry of Education Key Laboratory of Micro/Nano Systems for Aerospace, Northwestern Polytechnical University, Xi'an 710072, China
| | - Binghe Ma
- Ministry of Education Key Laboratory of Micro/Nano Systems for Aerospace, Northwestern Polytechnical University, Xi'an 710072, China
| | - Kai Tao
- Ministry of Education Key Laboratory of Micro/Nano Systems for Aerospace, Northwestern Polytechnical University, Xi'an 710072, China
| | - Zhi Zhang
- State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases, Department of Oral Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Seeram Ramakrishna
- Centre for Nanofibers and Nanotechnology, National University of Singapore, Singapore 117576, Singapore
| | - Weizheng Yuan
- Ministry of Education Key Laboratory of Micro/Nano Systems for Aerospace, Northwestern Polytechnical University, Xi'an 710072, China
| | - Tao Ye
- Ministry of Education Key Laboratory of Micro/Nano Systems for Aerospace, Northwestern Polytechnical University, Xi'an 710072, China
| |
Collapse
|
|
15
|
Ren Y, Zhang C, Liu Y, Kong W, Yang X, Niu H, Qiang L, Yang H, Yang F, Wang C, Wang J. Advances in 3D Printing of Highly Bioadaptive Bone Tissue Engineering Scaffolds. ACS Biomater Sci Eng 2024; 10:255-270. [PMID: 38118130 DOI: 10.1021/acsbiomaterials.3c01129] [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: 12/22/2023]
Abstract
The number of patients with bone defects caused by trauma, bone tumors, and osteoporosis has increased considerably. The repair of irregular, recurring, and large bone defects poses a great challenge to clinicians. Bone tissue engineering is emerging as an appropriate strategy to replace autologous bone grafting in the repair of critically sized bone defects. However, the suitability of bone tissue engineering scaffolds in terms of structure, mechanics, degradation, and the microenvironment is inadequate. Three-dimensional (3D) printing is an advanced additive-manufacturing technology widely used for bone repair. 3D printing constructs personalized structurally adapted scaffolds based on 3D models reconstructed from CT images. The contradiction between the mechanics and degradation is resolved by altering the stacking structure. The local microenvironment of the implant is improved by designing an internal pore structure and a spatiotemporal factor release system. Therefore, there has been a boom in the 3D printing of personalized bone repair scaffolds. In this review, successful research on the preparation of highly bioadaptive bone tissue engineering scaffolds using 3D printing is presented. The mechanisms of structural, mechanical, degradation, and microenvironmental adaptations of bone prostheses and their interactions were elucidated to provide a feasible strategy for constructing highly bioadaptive bone tissue engineering scaffolds.
Collapse
Affiliation(s)
- Ya Ren
- School of Rehabilitation Medicine, Weifang Medical University, Shandong 261041, China
- Southwest JiaoTong University College of Medicine, No. 111 North first Section of Second Ring Road, Chengdu 610036, China
- Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China
| | - Changru Zhang
- Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China
| | - Yihao Liu
- Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China
| | - Weiqing Kong
- Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao 266000, Shandong Province, China
| | - Xue Yang
- Southwest JiaoTong University College of Medicine, No. 111 North first Section of Second Ring Road, Chengdu 610036, China
| | - Haoyi Niu
- Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China
| | - Lei Qiang
- Key Laboratory of Advanced Technologies of Materials (Ministry of Education), School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, P. R. China
| | - Han Yang
- Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China
| | - Fei Yang
- Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China
| | - Chengwei Wang
- Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China
| | - Jinwu Wang
- School of Rehabilitation Medicine, Weifang Medical University, Shandong 261041, China
- Southwest JiaoTong University College of Medicine, No. 111 North first Section of Second Ring Road, Chengdu 610036, China
- Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China
| |
Collapse
|
|
16
|
Yeh SH, Yu JH, Chou PH, Wu SH, Liao YT, Huang YC, Chen TM, Wang JP. Proliferation and Differentiation Potential of Bone Marrow-Derived Mesenchymal Stem Cells From Children With Polydactyly and Adults With Basal Joint Arthritis. Cell Transplant 2024; 33:9636897231221878. [PMID: 38164917 PMCID: PMC10762874 DOI: 10.1177/09636897231221878] [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: 06/30/2023] [Revised: 11/20/2023] [Accepted: 12/06/2023] [Indexed: 01/03/2024] Open
Abstract
This study compared the proliferation and differentiation potential of bone marrow-derived mesenchymal stem cells (BMSCs) derived from infants with polydactyly and adults with basal joint arthritis. The proliferation rate of adult and infant BMSCs was determined by the cell number changes and doubling times. The γH2AX immunofluorescence staining, age-related gene expression, senescence-associated β-galactosidase (SA-β-gal) staining were analyzed to determine the senescence state of adult and infant BMSCs. The expression levels of superoxide dismutases (SODs) and genes associated with various types of differentiation were measured using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR). Differentiation levels were evaluated through histochemical and immunohistochemical staining. The results showed that infant BMSCs had a significantly higher increase in cell numbers and faster doubling times compared with adult BMSCs. Infant BMSCs at late stages exhibited reduced γH2AX expression and SA-β-gal staining, indicating lower levels of senescence. The expression levels of senescence-related genes (p16, p21, and p53) in infant BMSCs were also lower than in adult BMSCs. In addition, infant BMSCs demonstrated higher antioxidative ability with elevated expression of SOD1, SOD2, and SOD3 compared with adult BMSCs. In terms of differentiation potential, infant BMSCs outperformed adult BMSCs in chondrogenesis, as indicated by higher expression levels of chondrogenic genes (SOX9, COL2, and COL10) and positive immunohistochemical staining. Moreover, differentiated cells derived from infant BMSCs exhibited significantly higher expression levels of osteogenic, tenogenic, hepatogenic, and neurogenic genes compared with those derived from adult BMSCs. Histochemical and immunofluorescence staining confirmed these findings. However, adult BMSCs showed lower adipogenic differentiation potential compared with infant BMSCs. Overall, infant BMSCs demonstrated superior characteristics, including higher proliferation rates, enhanced antioxidative activity, and greater differentiation potential into various lineages. They also exhibited reduced cellular senescence. These findings, within the context of cellular differentiation, suggest potential implications for the use of allogeneic BMSC transplantation, emphasizing the need for further in vivo investigation.
Collapse
Affiliation(s)
- Shih-Han Yeh
- Department of Orthopedic Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan
| | - Jin-Huei Yu
- Department of Orthopedic Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan
| | - Po-Hsin Chou
- Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei
| | - Szu-Hsien Wu
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei
- Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, National Defense Medical Center, Taipei
| | - Yu-Ting Liao
- Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei
| | - Yi-Chao Huang
- Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei
| | - Tung-Ming Chen
- Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei
- Division of Orthopedics, Taipei City Hospital Zhongxiao Branch, Taipei
| | - Jung-Pan Wang
- Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei
| |
Collapse
|
|
17
|
Fang Q, Wei Y, Zhang Y, Cao W, Yan L, Kong M, Zhu Y, Xu Y, Guo L, Zhang L, Wang W, Yu Y, Sun J, Yang J. Stem cells as potential therapeutics for hearing loss. Front Neurosci 2023; 17:1259889. [PMID: 37746148 PMCID: PMC10512725 DOI: 10.3389/fnins.2023.1259889] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 08/23/2023] [Indexed: 09/26/2023] Open
Abstract
Hearing impairment is a global health problem. Stem cell therapy has become a cutting-edge approach to tissue regeneration. In this review, the recent advances in stem cell therapy for hearing loss have been discussed. Nanomaterials can modulate the stem cell microenvironment to augment the therapeutic effects further. The potential of combining nanomaterials with stem cells for repairing and regenerating damaged inner ear hair cells (HCs) and spiral ganglion neurons (SGNs) has also been discussed. Stem cell-derived exosomes can contribute to the repair and regeneration of damaged tissue, and the research progress on exosome-based hearing loss treatment has been summarized as well. Despite stem cell therapy's technical and practical limitations, the findings reported so far are promising and warrant further investigation for eventual clinical translation.
Collapse
Affiliation(s)
- Qiaojun Fang
- Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
- School of Life Sciences and Technology, Southeast University, Nanjing, China
| | - Yongjie Wei
- Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Yuhua Zhang
- Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Wei Cao
- Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Lin Yan
- Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Mengdie Kong
- School of Life Sciences and Technology, Southeast University, Nanjing, China
| | - Yongjun Zhu
- Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Yan Xu
- Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Lingna Guo
- Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Lei Zhang
- Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Weiqing Wang
- Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Yafeng Yu
- Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Jingwu Sun
- Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Jianming Yang
- Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| |
Collapse
|
|
18
|
Park JYC, King A, Björk V, English BW, Fedintsev A, Ewald CY. Strategic outline of interventions targeting extracellular matrix for promoting healthy longevity. Am J Physiol Cell Physiol 2023; 325:C90-C128. [PMID: 37154490 DOI: 10.1152/ajpcell.00060.2023] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 04/28/2023] [Accepted: 04/28/2023] [Indexed: 05/10/2023]
Abstract
The extracellular matrix (ECM), composed of interlinked proteins outside of cells, is an important component of the human body that helps maintain tissue architecture and cellular homeostasis. As people age, the ECM undergoes changes that can lead to age-related morbidity and mortality. Despite its importance, ECM aging remains understudied in the field of geroscience. In this review, we discuss the core concepts of ECM integrity, outline the age-related challenges and subsequent pathologies and diseases, summarize diagnostic methods detecting a faulty ECM, and provide strategies targeting ECM homeostasis. To conceptualize this, we built a technology research tree to hierarchically visualize possible research sequences for studying ECM aging. This strategic framework will hopefully facilitate the development of future research on interventions to restore ECM integrity, which could potentially lead to the development of new drugs or therapeutic interventions promoting health during aging.
Collapse
Affiliation(s)
- Ji Young Cecilia Park
- Laboratory of Extracellular Matrix Regeneration, Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zürich, Schwerzenbach, Switzerland
| | - Aaron King
- Foresight Institute, San Francisco, California, United States
| | | | - Bradley W English
- Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
| | | | - Collin Y Ewald
- Laboratory of Extracellular Matrix Regeneration, Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zürich, Schwerzenbach, Switzerland
| |
Collapse
|
|
19
|
Baouche M, Ochota M, Locatelli Y, Mermillod P, Niżański W. Mesenchymal Stem Cells: Generalities and Clinical Significance in Feline and Canine Medicine. Animals (Basel) 2023; 13:1903. [PMID: 37370414 DOI: 10.3390/ani13121903] [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] [Received: 03/31/2023] [Revised: 05/29/2023] [Accepted: 06/02/2023] [Indexed: 06/29/2023] Open
Abstract
Mesenchymal stem cells (MSCs) are multipotent cells: they can proliferate like undifferentiated cells and have the ability to differentiate into different types of cells. A considerable amount of research focuses on the potential therapeutic benefits of MSCs, such as cell therapy or tissue regeneration, and MSCs are considered powerful tools in veterinary regenerative medicine. They are the leading type of adult stem cells in clinical trials owing to their immunosuppressive, immunomodulatory, and anti-inflammatory properties, as well as their low teratogenic risk compared with pluripotent stem cells. The present review details the current understanding of the fundamental biology of MSCs. We focus on MSCs' properties and their characteristics with the goal of providing an overview of therapeutic innovations based on MSCs in canines and felines.
Collapse
Affiliation(s)
- Meriem Baouche
- Department of Reproduction and Clinic of Farm Animals, Wrocław University of Environmental and Life Sciences, 50-366 Wrocław, Poland
| | - Małgorzata Ochota
- Department of Reproduction and Clinic of Farm Animals, Wrocław University of Environmental and Life Sciences, 50-366 Wrocław, Poland
| | - Yann Locatelli
- Physiology of Reproduction and Behaviors (PRC), UMR085, INRAE, CNRS, University of Tours, 37380 Nouzilly, France
- Museum National d'Histoire Naturelle, Réserve Zoologique de la Haute Touche, 36290 Obterre, France
| | - Pascal Mermillod
- Physiology of Reproduction and Behaviors (PRC), UMR085, INRAE, CNRS, University of Tours, 37380 Nouzilly, France
| | - Wojciech Niżański
- Department of Reproduction and Clinic of Farm Animals, Wrocław University of Environmental and Life Sciences, 50-366 Wrocław, Poland
| |
Collapse
|
|
20
|
Xia Y, Geng N, Ren J, Liao C, Wang M, Chen S, Chen H, Peng W. Regulation of endothelial cells on the osteogenic ability of bone marrow mesenchymal stem cells in peri-implantitis. Tissue Cell 2023; 81:102042. [PMID: 36812664 DOI: 10.1016/j.tice.2023.102042] [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: 10/20/2022] [Revised: 01/16/2023] [Accepted: 02/16/2023] [Indexed: 02/19/2023]
Abstract
OBJECTIVES The relationship between bone resorption and angiogenesis in peri-implantitis remains to be studied. We constructed a Beagle dog model of peri-implantitis, and extracted bone marrow mesenchymal stem cells (BMSCs) and endothelial cells (ECs) for culture. The osteogenic ability of BMSCs in the presence of ECs was investigated through an in vitro osteogenic induction model, and its mechanism was initially explored. SUBJECTS AND METHODS The peri-implantitis model was verified by ligation, bone loss was observed by micro-CT, and cytokines were detected by ELISA. The isolated BMSCs and ECs were cultured to detect the expression of angiogenesis, osteogenesis-related proteins, and NF-κB signaling pathway-related proteins. RESULTS 8 weeks after surgery, the peri-implant gums were swollen, and micro-CT showed bone resorption. Compared with the control group, IL-1β, TNF-α, ANGII and VEGF were markedly increased in the peri-implantitis group. In vitro studies found that the osteogenic differentiation ability of BMSCs co-cultured with IECs was decreased, and the expression of NF-κB signaling pathway-related cytokines was increased. CONCLUSION Endothelial cells inhibit the osteogenic differentiation of bone marrow mesenchymal stem cells through NF-κB signaling in the environment of peri-implantitis, which may become a new target for the treatment of peri-implantitis.
Collapse
Affiliation(s)
- Yixin Xia
- Department of Stomatology, The First Affiliated Hospital, Sun Yat-sen University, China
| | - Ningbo Geng
- Department of Stomatology, The First Affiliated Hospital, Sun Yat-sen University, China
| | - Jing Ren
- Department of Stomatology, The First Affiliated Hospital, Sun Yat-sen University, China
| | - Chunhui Liao
- Department of Orthodontics, Guangzhou Women and Children's Medical Center, Guangzhou, China
| | - Ming Wang
- Department of Stomatology, The First Affiliated Hospital, Sun Yat-sen University, China
| | - Songling Chen
- Department of Stomatology, The First Affiliated Hospital, Sun Yat-sen University, China
| | - Huanlin Chen
- Department of Stomatology, Huizhou Municipal Central Hospital, Huizhou, China
| | - Wei Peng
- Department of Stomatology, The First Affiliated Hospital, Sun Yat-sen University, China.
| |
Collapse
|
|
21
|
Kuca-Warnawin E, Kurowska W, Plebańczyk M, Wajda A, Kornatka A, Burakowski T, Janicka I, Syrówka P, Skalska U. Basic Properties of Adipose-Derived Mesenchymal Stem Cells of Rheumatoid Arthritis and Osteoarthritis Patients. Pharmaceutics 2023; 15:pharmaceutics15031003. [PMID: 36986863 PMCID: PMC10051260 DOI: 10.3390/pharmaceutics15031003] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Revised: 03/10/2023] [Accepted: 03/17/2023] [Indexed: 03/30/2023] Open
Abstract
Rheumatoid arthritis (RA) and osteoarthritis (OA) are destructive joint diseases, the development of which are associated with the expansion of pathogenic T lymphocytes. Mesenchymal stem cells may be an attractive therapeutic option for patients with RA or OA due to the regenerative and immunomodulatory abilities of these cells. The infrapatellar fat pad (IFP) is a rich and easily available source of mesenchymal stem cells (adipose-derived stem cells, ASCs). However, the phenotypic, potential and immunomodulatory properties of ASCs have not been fully characterised. We aimed to evaluate the phenotype, regenerative potential and effects of IFP-derived ASCs from RA and OA patients on CD4+ T cell proliferation. The MSC phenotype was assessed using flow cytometry. The multipotency of MSCs was evaluated on the basis of their ability to differentiate into adipocytes, chondrocytes and osteoblasts. The immunomodulatory activities of MSCs were examined in co-cultures with sorted CD4+ T cells or peripheral blood mononuclear cells. The concentrations of soluble factors involved in ASC-dependent immunomodulatory activities were assessed in co-culture supernatants using ELISA. We found that ASCs with PPIs from RA and OA patients maintain the ability to differentiate into adipocytes, chondrocytes and osteoblasts. ASCs from RA and OA patients also showed a similar phenotype and comparable abilities to inhibit CD4+ T cell proliferation, which was dependent on the induction of soluble factors The results of our study constitute the basis for further research on the therapeutic potential of ASCs in the treatment of patients with RA and OA.
Collapse
Affiliation(s)
- Ewa Kuca-Warnawin
- Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland
| | - Weronika Kurowska
- Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland
| | - Magdalena Plebańczyk
- Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland
| | - Anna Wajda
- Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland
| | - Anna Kornatka
- Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland
| | - Tomasz Burakowski
- Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland
| | - Iwona Janicka
- Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland
| | - Piotr Syrówka
- Rheumaorthopedics Clinic and Polyclinic, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland
| | - Urszula Skalska
- Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland
| |
Collapse
|
|
22
|
Sood A, Kumar A, Gupta VK, Kim CM, Han SS. Translational Nanomedicines Across Human Reproductive Organs Modeling on Microfluidic Chips: State-of-the-Art and Future Prospects. ACS Biomater Sci Eng 2023; 9:62-84. [PMID: 36541361 DOI: 10.1021/acsbiomaterials.2c01080] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Forecasting the consequence of nanoparticles (NPs) and therapeutically significant molecules before materializing for human clinical trials is a mainstay for drug delivery and screening processes. One of the noteworthy obstacles that has prevented the clinical translation of NP-based drug delivery systems and novel drugs is the lack of effective preclinical platforms. As a revolutionary technology, the organ-on-a-chip (OOC), a coalition of microfluidics and tissue engineering, has surfaced as an alternative to orthodox screening platforms. OOC technology recapitulates the structural and physiological features of human organs along with intercommunications between tissues on a chip. The current review discusses the concept of microfluidics and confers cutting-edge fabrication processes for chip designing. We also outlined the advantages of microfluidics in analyzing NPs in terms of characterization, transport, and degradation in biological systems. The review further elaborates the scope and research on translational nanomedicines in human reproductive organs (testis, placenta, uterus, and menstrual cycle) by taking the advantages offered by microfluidics and shedding light on their potential future implications. Finally, we accentuate the existing challenges for clinical translation and scale-up dynamics for microfluidics chips and emphasize its future perspectives.
Collapse
Affiliation(s)
- Ankur Sood
- School of Chemical Engineering, Yeungnam University, 280 Daehak-ro, Gyeongsan 38541, South Korea
| | - Anuj Kumar
- School of Chemical Engineering, Yeungnam University, 280 Daehak-ro, Gyeongsan 38541, South Korea.,Institute of Cell Culture, Yeungnam University, 280 Daehak-ro, Gyeongsan 38541, South Korea
| | - Vijai Kumar Gupta
- Biorefining and Advanced Materials Research Center, Scotland's Rural College, Edinburgh EH9 3JG, United Kingdom
| | - Chul Min Kim
- Department of Mechatronics Engineering, Gyeongsang National University, 33 Dongjin-ro, Jinju, Gyeongsangnam-do 52725, South Korea
| | - Sung Soo Han
- School of Chemical Engineering, Yeungnam University, 280 Daehak-ro, Gyeongsan 38541, South Korea.,Institute of Cell Culture, Yeungnam University, 280 Daehak-ro, Gyeongsan 38541, South Korea
| |
Collapse
|
|
23
|
Politakos N. Block Copolymers in 3D/4D Printing: Advances and Applications as Biomaterials. Polymers (Basel) 2023; 15:polym15020322. [PMID: 36679203 PMCID: PMC9864278 DOI: 10.3390/polym15020322] [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: 11/29/2022] [Revised: 01/03/2023] [Accepted: 01/04/2023] [Indexed: 01/11/2023] Open
Abstract
3D printing is a manufacturing technique in constant evolution. Day by day, new materials and methods are discovered, making 3D printing continually develop. 3D printers are also evolving, giving us objects with better resolution, faster, and in mass production. One of the areas in 3D printing that has excellent potential is 4D printing. It is a technique involving materials that can react to an environmental stimulus (pH, heat, magnetism, humidity, electricity, and light), causing an alteration in their physical or chemical state and performing another function. Lately, 3D/4D printing has been increasingly used for fabricating materials aiming at drug delivery, scaffolds, bioinks, tissue engineering (soft and hard), synthetic organs, and even printed cells. The majority of the materials used in 3D printing are polymeric. These materials can be of natural origin or synthetic ones of different architectures and combinations. The use of block copolymers can combine the exemplary properties of both blocks to have better mechanics, processability, biocompatibility, and possible stimulus behavior via tunable structures. This review has gathered fundamental aspects of 3D/4D printing for biomaterials, and it shows the advances and applications of block copolymers in the field of biomaterials over the last years.
Collapse
Affiliation(s)
- Nikolaos Politakos
- POLYMAT, Applied Chemistry Department, Faculty of Chemistry, University of the Basque Country, UPV/EHU, Paseo Manuel de Lardizabal 3, 20018 Donostia-San Sebastián, Spain
| |
Collapse
|
|
24
|
Anwar I, Ashfaq UA. Impact of Nanotechnology on Differentiation and Augmentation of Stem Cells for Liver Therapy. Crit Rev Ther Drug Carrier Syst 2023; 40:89-116. [PMID: 37585310 DOI: 10.1615/critrevtherdrugcarriersyst.2023042400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/18/2023]
Abstract
The liver is one of the crucial organs of the body that performs hundreds of chemical reactions needed by the body to survive. It is also the largest gland of the body. The liver has multiple functions, including the synthesis of chemicals, metabolism of nutrients, and removal of toxins. It also acts as a storage unit. The liver has a unique ability to regenerate itself, but it can lead to permanent damage if the injury is beyond recovery. The only possible treatment of severe liver damage is liver transplant which is a costly procedure and has several other drawbacks. Therefore, attention has been shifted towards the use of stem cells that have shown the ability to differentiate into hepatocytes. Among the numerous kinds of stem cells (SCs), the mesenchymal stem cells (MSCs) are the most famous. Various studies suggest that an MSC transplant can repair liver function, improve the signs and symptoms, and increase the chances of survival. This review discusses the impact of combining stem cell therapy with nanotechnology. By integrating stem cell science and nanotechnology, the information about stem cell differentiation and regulation will increase, resulting in a better comprehension of stem cell-based treatment strategies. The augmentation of SCs with nanoparticles has been shown to boost the effect of stem cell-based therapy. Also, the function of green nanoparticles in liver therapies is discussed.
Collapse
Affiliation(s)
- Ifrah Anwar
- Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Faisalabad, Pakistan
| | - Usman Ali Ashfaq
- Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Faisalabad, Pakistan
| |
Collapse
|
|
25
|
Hassan TA, Maher MA, El Karmoty AF, Ahmed ZSO, Ibrahim MA, Rizk H, Reyad AT. Auricular cartilage regeneration using different types of mesenchymal stem cells in rabbits. Biol Res 2022; 55:40. [PMID: 36572914 PMCID: PMC9791760 DOI: 10.1186/s40659-022-00408-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 12/13/2022] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Cartilaginous disorders comprise a wide range of diseases that affect normal joint movement, ear and nose shape; and they have great social and economic impact. Mesenchymal stem cells (MSCs) provide a promising regeneration alternative for treatment of degenerative cartilaginous disorders. This study aimed to compare therapeutic potential of different types of laser activated MSCs to promote auricular cartilage regeneration. Twelve adult rabbit allocated equally in four groups, all animals received a surgical mid auricular cartilage defect in one ear; Group I (Positive control) injected sub-perichondrially with phosphate-buffered saline (PBS), Group II (ADMSC-transplanted group) injected adipose-derived MSCs (ADMSCs), Group III (BMMSCs-transplanted group) received bone marrow-derived MSCs (BMMSCs), and Group IV (EMSC-transplanted group) received ear MSCs (EMSCs) in the defected ear. The auricular defect was analyzed morphologically, histopathologically and immunohistochemically after 4 weeks. In addition, a quantitative real-time polymerase chain reaction was used to examine expression of the collagen type II (Col II) and aggrecan as cartilage growth factors. RESULTS The auricles of all treatments appeared completely healed with smooth surfaces and similar tissue color. Histopathologically, defective areas of control positive group, ADMSCs and EMSCs treated groups experienced a small area of immature cartilage. While BMMSCs treated group exhibited typical features of new cartilage formation with mature chondrocytes inside their lacunae and dense extracellular matrix (ECM). In addition, BMMSC treated group showed a positive reaction to Masson's trichrome and orcein stains. In contrary, control positive, ADMSC and EMSC groups revealed faint staining with Masson's trichrome and Orcein. Immunohistochemically, there was an intense positive S100 expression in BMMSCs (with a significant increase of area percentage + 21.89 (P < 0.05), a moderate reaction in EMSCs (with an area percentage + 17.97, and a mild reaction in the control group and ADMSCs (area percentages + 8.02 and + 11.37, respectively). The expression of relative col II and aggrecan was substantially highest in BMMSCs (± 0.91 and ± 0.89, respectively). While, Control positive, ADMSCs and EMSCs groups recorded (± 0.41: ± 0.21, ± 0.6: ± 0.44, ± 0.61: ± 0.63) respectively. CONCLUSION BMMSCs showed the highest chondrogenic potential compared to ADMSCs and EMSCs and should be considered the first choice in treatment of cartilaginous degenerative disorders.
Collapse
Affiliation(s)
- Taghreed Ahmed Hassan
- grid.7776.10000 0004 0639 9286Anatomy and Embryology Department, Faculty of Veterinary Medicine, Cairo University, Giza Square, Giza, 12211 Egypt
| | - Mohamed Ahmed Maher
- grid.7776.10000 0004 0639 9286Anatomy and Embryology Department, Faculty of Veterinary Medicine, Cairo University, Giza Square, Giza, 12211 Egypt
| | - Amr Fekry El Karmoty
- grid.7776.10000 0004 0639 9286Anatomy and Embryology Department, Faculty of Veterinary Medicine, Cairo University, Giza Square, Giza, 12211 Egypt
| | - Zainab Sabry Othman Ahmed
- grid.7776.10000 0004 0639 9286Cytology and Histology Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt ,King Salman International University, South Sinai, Ras Sudr, Egypt
| | - Marwa A Ibrahim
- grid.7776.10000 0004 0639 9286Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Cairo University, Giza Square, Giza, 12211 Egypt
| | - Hamdy Rizk
- grid.7776.10000 0004 0639 9286Anatomy and Embryology Department, Faculty of Veterinary Medicine, Cairo University, Giza Square, Giza, 12211 Egypt
| | - Ayman Tolba Reyad
- grid.7776.10000 0004 0639 9286Anatomy and Embryology Department, Faculty of Veterinary Medicine, Cairo University, Giza Square, Giza, 12211 Egypt
| |
Collapse
|
|
26
|
Kim SD, Cho KS. Immunomodulatory Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Allergic Airway Disease. LIFE (BASEL, SWITZERLAND) 2022; 12:life12121994. [PMID: 36556359 PMCID: PMC9786036 DOI: 10.3390/life12121994] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 11/23/2022] [Accepted: 11/25/2022] [Indexed: 12/03/2022]
Abstract
Mesenchymal stem cells (MSCs) have been reported as promising candidates for the treatment of various diseases, especially allergic diseases, as they have the capacity to differentiate into various cells. However, MSCs itself have several limitations such as creating a risk of aneuploidy, difficulty in handling them, immune rejection, and tumorigenicity, so interest in the extracellular vesicles (EVs) released from MSCs are increasing, and many studies have been reported. Previous studies have shown that extracellular vesicles (EVs) produced by MSCs are as effective as the MSCs themselves in suppression of allergic airway inflammation through the suppression of Th2 cytokine production and the induction of regulatory T cells (Treg) expansion. EVs are one of the substances secreted by paracrine induction from MSCs, and because it exerts its effect by delivering contents such as mRNA, microRNA, and proteins to the receptor cell, it can reduce the problems or risks related to stem cell therapy. This article reviews the immunomodulatory properties of MSCs-derived EVs and their therapeutic implications for allergic airway disease.
Collapse
Affiliation(s)
- Sung-Dong Kim
- Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University School of Medicine, Pusan National University Hospital, 179 Gudeok-Ro, Seo-gu, Busan 602-739, Republic of Korea
| | - Kyu-Sup Cho
- Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University School of Medicine, Pusan National University Hospital, 179 Gudeok-Ro, Seo-gu, Busan 602-739, Republic of Korea
| |
Collapse
|
|
27
|
Stem cell membrane-coated abiotic nanomaterials for biomedical applications. J Control Release 2022; 351:174-197. [PMID: 36103910 DOI: 10.1016/j.jconrel.2022.09.012] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 09/06/2022] [Accepted: 09/07/2022] [Indexed: 12/15/2022]
Abstract
Nanoscale materials have been extensively employed for diagnostic and therapeutic purposes. However, the developed nanosystems still suffer from some limitations, namely the rapid elimination by the immune system, lack of targeting to specific cells, and insufficient biocompatibility. Therefore, novel strategies based upon a biomimetic approach have received attention to improving the pharmacokinetics and safety profile of nanosystems. One promising strategy is the application of a biomimetic coating consisting of cell membranes derived from different cell types onto nanoparticle cores. Stem cells have been investigated to develop targeted nanodevices owing to their excellent intrinsic tissue-specific homing features, protecting them from the immune system to reach the sites of inflammation. This targeting ability is conferred by a surface repertoire of stem cell-associated biomolecules. Such nanoscopical materials offer sustained circulation and boosted drug accumulation at target sites, augmenting therapeutic efficacy and safety. Additionally, the coating of nanoparticles with cell membranes acts as a camouflage mechanism to increase their circulation time. The current review explores the particular features of stem cell membrane coating as multifunctional biomimetic surface functionalization agents to camouflage nanoparticle cores. Biomedical applications of engineered stem cell membrane-coated nanoparticles, challenges in clinical translation, and their future prospects are addressed.
Collapse
|
|
28
|
Nunes HC, Tavares SC, Garcia HV, Cucielo MS, Dos Santos SAA, Aal MCE, de Golim MA, Justulin LA, Ribeiro AO, Deffune E, Scarano WR, Delella FK. Bisphenol A and 2,3,7,8-tetrachlorodibenzo-p-dioxin at non-cytotoxic doses alter the differentiation potential and cell function of rat adipose-stem cells. ENVIRONMENTAL TOXICOLOGY 2022; 37:2314-2323. [PMID: 35661558 DOI: 10.1002/tox.23598] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 04/19/2022] [Accepted: 05/21/2022] [Indexed: 06/15/2023]
Abstract
The possibility of chemical contamination is an important issue to consider when designing a cell therapy strategy. Both bisphenol A (BPA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are among the most environmentally relevant endocrine disrupting chemicals (EDCs, compounds with a high affinity for adipose tissue) recently studied. Adipose-derived stem cells (ASCs) are mesenchymal stromal cells (MSCs) obtained from adipose tissue widely used in regenerative medicine to prevent and treat diseases in several tissues and organs. Although the experimental use of tissue-engineered constructs requires careful analysis for approval and implantation, there has been a recent increase in the number of approved clinical trials for this promising strategy. This study aimed to evaluate cell viability, apoptosis, DNA damage, and the adipogenic or osteogenic differentiation potential of rat adipose-derived stem cells (rASCs) exposed to previously established non-cytotoxic doses of BPA and TCDD in vitro. Results demonstrated that 10 μM of BPA and 10 nM of TCDD were able to significantly reduce cell viability, while all exposure levels resulted in DNA damage, although did not increase the apoptosis rate. According to the analysis of adipogenic differentiation, 1 μM of BPA induced the significant formation of oil droplets, suggesting an increased adipocyte differentiation, while both 10 μM of BPA and 10 nM of TCDD decreased adipocyte differentiation. Osteogenic differentiation did not differ among the treatments. As such, BPA and TCDD in the concentrations tested can modify important processes in rASCs such as cell viability, adipogenic differentiation, and DNA damage. Together, these findings prove that EDCs play an important role as contaminants, putatively interfering in cell differentiation and thus impairing the therapeutic use of ASCs.
Collapse
Affiliation(s)
- Helga Caputo Nunes
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil
| | - Samara Costa Tavares
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil
| | - Heloísa Vicente Garcia
- Botucatu Medical School, Blood Transfusion Center, Cell Engineering Lab, São Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil
| | - Maira Smaniotto Cucielo
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil
| | | | - Mirian Carolini Esgoti Aal
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil
| | - Marjorie Assis de Golim
- Botucatu Medical School, Blood Transfusion Center, Flow Cytometry Laboratory, São Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil
| | - Luís Antônio Justulin
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil
| | - Amanda Oliveira Ribeiro
- Department of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil
| | - Elenice Deffune
- Botucatu Medical School, Blood Transfusion Center, Cell Engineering Lab, São Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil
| | - Wellerson Rodrigo Scarano
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil
| | - Flávia Karina Delella
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil
| |
Collapse
|
|
29
|
Hoang DM, Pham PT, Bach TQ, Ngo ATL, Nguyen QT, Phan TTK, Nguyen GH, Le PTT, Hoang VT, Forsyth NR, Heke M, Nguyen LT. Stem cell-based therapy for human diseases. Signal Transduct Target Ther 2022; 7:272. [PMID: 35933430 PMCID: PMC9357075 DOI: 10.1038/s41392-022-01134-4] [Citation(s) in RCA: 435] [Impact Index Per Article: 145.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 07/19/2022] [Accepted: 07/21/2022] [Indexed: 02/07/2023] Open
Abstract
Recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be treated. Stem cell-based therapy, including human pluripotent stem cells (hPSCs) and multipotent mesenchymal stem cells (MSCs), has recently emerged as a key player in regenerative medicine. hPSCs are defined as self-renewable cell types conferring the ability to differentiate into various cellular phenotypes of the human body, including three germ layers. MSCs are multipotent progenitor cells possessing self-renewal ability (limited in vitro) and differentiation potential into mesenchymal lineages, according to the International Society for Cell and Gene Therapy (ISCT). This review provides an update on recent clinical applications using either hPSCs or MSCs derived from bone marrow (BM), adipose tissue (AT), or the umbilical cord (UC) for the treatment of human diseases, including neurological disorders, pulmonary dysfunctions, metabolic/endocrine-related diseases, reproductive disorders, skin burns, and cardiovascular conditions. Moreover, we discuss our own clinical trial experiences on targeted therapies using MSCs in a clinical setting, and we propose and discuss the MSC tissue origin concept and how MSC origin may contribute to the role of MSCs in downstream applications, with the ultimate objective of facilitating translational research in regenerative medicine into clinical applications. The mechanisms discussed here support the proposed hypothesis that BM-MSCs are potentially good candidates for brain and spinal cord injury treatment, AT-MSCs are potentially good candidates for reproductive disorder treatment and skin regeneration, and UC-MSCs are potentially good candidates for pulmonary disease and acute respiratory distress syndrome treatment.
Collapse
Affiliation(s)
- Duc M Hoang
- Department of Research and Development, Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam.
| | - Phuong T Pham
- Department of Cellular Therapy, Vinmec High-Tech Center, Vinmec Healthcare System, Hanoi, Vietnam
| | - Trung Q Bach
- Department of Research and Development, Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam
| | - Anh T L Ngo
- Department of Cellular Therapy, Vinmec High-Tech Center, Vinmec Healthcare System, Hanoi, Vietnam
| | - Quyen T Nguyen
- Department of Research and Development, Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam
| | - Trang T K Phan
- Department of Research and Development, Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam
| | - Giang H Nguyen
- Department of Research and Development, Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam
| | - Phuong T T Le
- Department of Research and Development, Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam
| | - Van T Hoang
- Department of Research and Development, Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam
| | - Nicholas R Forsyth
- Institute for Science & Technology in Medicine, Keele University, Keele, UK
| | - Michael Heke
- Department of Biology, Stanford University, Stanford, CA, USA
| | - Liem Thanh Nguyen
- Department of Research and Development, Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam
| |
Collapse
|
|
30
|
Dozzo A, Galvin A, Shin JW, Scalia S, O'Driscoll CM, Ryan KB. Modelling acute myeloid leukemia (AML): What's new? A transition from the classical to the modern. Drug Deliv Transl Res 2022:10.1007/s13346-022-01189-4. [PMID: 35930221 DOI: 10.1007/s13346-022-01189-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/24/2022] [Indexed: 11/24/2022]
Abstract
Acute myeloid leukemia (AML) is a heterogeneous malignancy affecting myeloid cells in the bone marrow (BM) but can spread giving rise to impaired hematopoiesis. AML incidence increases with age and is associated with poor prognostic outcomes. There has been a disconnect between the success of novel drug compounds observed in preclinical studies of hematological malignancy and less than exceptional therapeutic responses in clinical trials. This review aims to provide a state-of-the-art overview on the different preclinical models of AML available to expand insights into disease pathology and as preclinical screening tools. Deciphering the complex physiological and pathological processes and developing predictive preclinical models are key to understanding disease progression and fundamental in the development and testing of new effective drug treatments. Standard scaffold-free suspension models fail to recapitulate the complex environment where AML occurs. To this end, we review advances in scaffold/matrix-based 3D models and outline the most recent advances in on-chip technology. We also provide an overview of clinically relevant animal models and review the expanding use of patient-derived samples, which offer the prospect to create more "patient specific" screening tools either in the guise of 3D matrix models, microphysiological "organ-on-chip" tools or xenograft models and discuss representative examples.
Collapse
Affiliation(s)
| | - Aoife Galvin
- School of Pharmacy, University College Cork, Cork, Ireland
| | - Jae-Won Shin
- Department of Pharmacology and Regenerative Medicine, University of Illinois at Chicago College of Medicine, 909 S. Wolcott Ave, Chicago, IL, 5091 COMRB, USA
| | - Santo Scalia
- Università degli Studi di Ferrara, Via Luigi Borsari 46, 44121, Ferrara, Italy
| | - Caitriona M O'Driscoll
- School of Pharmacy, University College Cork, Cork, Ireland.,SSPC Centre for Pharmaceutical Research, School of Pharmacy, University College Cork, Cork, Ireland
| | - Katie B Ryan
- School of Pharmacy, University College Cork, Cork, Ireland. .,SSPC Centre for Pharmaceutical Research, School of Pharmacy, University College Cork, Cork, Ireland.
| |
Collapse
|
|
31
|
Song Y, Jorgensen C. Mesenchymal Stromal Cells in Osteoarthritis: Evidence for Structural Benefit and Cartilage Repair. Biomedicines 2022; 10:biomedicines10061278. [PMID: 35740299 PMCID: PMC9219878 DOI: 10.3390/biomedicines10061278] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 05/24/2022] [Accepted: 05/28/2022] [Indexed: 12/15/2022] Open
Abstract
Osteoarthritis (OA) presents a major clinical challenge to rheumatologists and orthopedists due to the lack of available drugs reducing structural degradation. Mesenchymal stromal cells (MSCs) may represent new therapeutic approaches in cartilage regeneration. In this review, we highlight the latest knowledge on the biological properties of MSC, such as their chondrogenic and immunomodulatory potential, and we give a brief overview of the effects of MSCs in preclinical and clinical studies of OA treatment and also compare different MSC sources, with the adipose tissue-derived MSCs being promising. Then, we focus on their structural benefit in treating OA and summarize the current evidence for the assessment of cartilage in OA according to magnetic resonance imaging (MRI) and second-look arthroscopy after MSC therapy. Finally, this review provides a brief perspective on enhancing the activity of MSCs.
Collapse
|
|
32
|
Three-Dimensional (3D) Printing in Cancer Therapy and Diagnostics: Current Status and Future Perspectives. Pharmaceuticals (Basel) 2022; 15:ph15060678. [PMID: 35745597 PMCID: PMC9229198 DOI: 10.3390/ph15060678] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 05/23/2022] [Accepted: 05/25/2022] [Indexed: 12/10/2022] Open
Abstract
Three-dimensional (3D) printing is a technique where the products are printed layer-by-layer via a series of cross-sectional slices with the exact deposition of different cell types and biomaterials based on computer-aided design software. Three-dimensional printing can be divided into several approaches, such as extrusion-based printing, laser-induced forward transfer-based printing systems, and so on. Bio-ink is a crucial tool necessary for the fabrication of the 3D construct of living tissue in order to mimic the native tissue/cells using 3D printing technology. The formation of 3D software helps in the development of novel drug delivery systems with drug screening potential, as well as 3D constructs of tumor models. Additionally, several complex structures of inner tissues like stroma and channels of different sizes are printed through 3D printing techniques. Three-dimensional printing technology could also be used to develop therapy training simulators for educational purposes so that learners can practice complex surgical procedures. The fabrication of implantable medical devices using 3D printing technology with less risk of infections is receiving increased attention recently. A Cancer-on-a-chip is a microfluidic device that recreates tumor physiology and allows for a continuous supply of nutrients or therapeutic compounds. In this review, based on the recent literature, we have discussed various printing methods for 3D printing and types of bio-inks, and provided information on how 3D printing plays a crucial role in cancer management.
Collapse
|
|
33
|
Wu SH, Yu JH, Liao YT, Liu KH, Chiang ER, Chang MC, Wang JP. Comparison of the Infant and Adult Adipose-Derived Mesenchymal Stem Cells in Proliferation, Senescence, Anti-oxidative Ability and Differentiation Potential. Tissue Eng Regen Med 2022; 19:589-601. [PMID: 35247199 PMCID: PMC9130449 DOI: 10.1007/s13770-022-00431-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 12/26/2021] [Accepted: 01/05/2022] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Infant adipose-derived mesenchymal stem cells (ADSCs) collected from excised polydactyly fat tissue, which was surgical waste, could be cultured and expanded in vitro in this study. In addition, the collecting process would not cause pain in the host. In this study, the proliferation, reduction of senescence, anti-oxidative ability, and differentiation potential in the infant ADSCs were compared with those in the adult ADSCs harvested from thigh liposuction to determine the availability of infant ADSCs. METHODS Proliferation was determined by detecting the fold changes in cell numbers and doubling time periods. Senescence was analyzed by investigating the age-related gene expression levels and the replicative stress. The superoxide dismutase (SOD) gene expression, adipogenic, neurogenic, osteogenic, and tenogenic differentiation were compared by RT-qPCR. The chondrogenic differentiation efficiency was also determined using RT-qPCR and immunohistochemical staining. RESULTS The proliferation, SOD (SOD1, SOD2 and SOD3) gene expression, the stemness-related gene (c-MYC) and telomerase reverse transcriptase of the infant ADSCs at early passages were enhanced compared with those of the adults'. Cellular senescence related genes, including p16, p21 and p53, and replicative stress were reduced in the infant ADSCs. The adipogenic genes (PPARγ and LPL) and neurogenic genes (MAP2 and NEFH) of the infant ADSC differentiated cells were significantly higher than those of the adults' while the expression of the osteogenic genes (OCN and RUNX) and tenogenic genes (TNC and COL3A1) of both demonstrated opposite results. The chondrogenic markers (SOX9, COL2 and COL10) were enhanced in the infant ADSC differentiated chondrogenic pellets, and the expression levels of SODs were decreased during the differentiation process. CONCLUSION Cultured infant ADSCs demonstrate less cellular senescence and replicative stress, higher proliferation rates, better antioxidant defense activity, and higher potential of chondrogenic, adipogenic and neurogenic differentiation.
Collapse
Affiliation(s)
- Szu-Hsien Wu
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, 112 Taiwan ,Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112 Taiwan ,Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, National Defense Medical Center, Taipei, Taiwan
| | - Jin-Huei Yu
- Department of Orthopedic Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, 33004 Taiwan
| | - Yu-Ting Liao
- Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei, 112 Taiwan
| | - Kuo-Hao Liu
- Department of Orthopaedics, National Yang Ming Chiao Tung University Hospital, Yilan, 260 Taiwan
| | - En-Rung Chiang
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112 Taiwan ,Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei, 112 Taiwan
| | - Ming-Chau Chang
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112 Taiwan ,Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei, 112 Taiwan
| | - Jung-pan Wang
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112 Taiwan ,Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei, 112 Taiwan
| |
Collapse
|
|
34
|
van Santen VJB, Bastidas Coral AP, Hogervorst JMA, Klein-Nulend J, Bakker AD. Biologically Relevant In Vitro 3D-Model to Study Bone Regeneration Potential of Human Adipose Stem Cells. Biomolecules 2022; 12:biom12020169. [PMID: 35204670 PMCID: PMC8961519 DOI: 10.3390/biom12020169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 01/14/2022] [Accepted: 01/18/2022] [Indexed: 11/16/2022] Open
Abstract
Standard cell cultures may not predict the proliferation and differentiation potential of human mesenchymal stromal cells (MSCs) after seeding on a scaffold and implanting this construct in a bone defect. We aimed to develop a more biologically relevant in vitro 3D-model for preclinical studies on the bone regeneration potential of MSCs. Human adipose tissue-derived mesenchymal stromal cells (hASCs; five donors) were seeded on biphasic calcium phosphate (BCP) granules and cultured under hypoxia (1% O2) for 14 days with pro-inflammatory TNFα, IL4, IL6, and IL17F (10 mg/mL each) added during the first three days, simulating the early stages of repair (bone construct model). Alternatively, hASCs were cultured on plastic, under 20% O2 and without cytokines for 14 days (standard cell culture). After two days, the bone construct model decreased total DNA (3.9-fold), COL1 (9.8-fold), and RUNX2 expression (19.6-fold) and metabolic activity (4.6-fold), but increased VEGF165 expression (38.6-fold) in hASCs compared to standard cultures. After seven days, the bone construct model decreased RUNX2 expression (64-fold) and metabolic activity (2.3-fold), but increased VEGF165 (54.5-fold) and KI67 expression (5.7-fold) in hASCs compared to standard cultures. The effect of the bone construct model on hASC proliferation and metabolic activity could be largely mimicked by culturing on BCP alone (20% O2, no cytokines). The effect of the bone construct model on VEGF165 expression could be mimicked by culturing hASCs under hypoxia alone (plastic, no cytokines). In conclusion, we developed a new, biologically relevant in vitro 3D-model to study the bone regeneration potential of MSCs. Our model is likely more suitable for the screening of novel factors to enhance bone regeneration than standard cell cultures.
Collapse
|
|
35
|
Samanipour R, Tahmooressi H, Rezaei Nejad H, Hirano M, Shin SR, Hoorfar M. A review on 3D printing functional brain model. BIOMICROFLUIDICS 2022; 16:011501. [PMID: 35145569 PMCID: PMC8816519 DOI: 10.1063/5.0074631] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Accepted: 12/31/2021] [Indexed: 05/08/2023]
Abstract
Modern neuroscience increasingly relies on 3D models to study neural circuitry, nerve regeneration, and neural disease. Several different biofabrication approaches have been explored to create 3D neural tissue model structures. Among them, 3D bioprinting has shown to have great potential to emerge as a high-throughput/high precision biofabrication strategy that can address the growing need for 3D neural models. Here, we have reviewed the design principles for neural tissue engineering. The main challenge to adapt printing technologies for biofabrication of neural tissue models is the development of neural bioink, i.e., a biomaterial with printability and gelation properties and also suitable for neural tissue culture. This review shines light on a vast range of biomaterials as well as the fundamentals of 3D neural tissue printing. Also, advances in 3D bioprinting technologies are reviewed especially for bioprinted neural models. Finally, the techniques used to evaluate the fabricated 2D and 3D neural models are discussed and compared in terms of feasibility and functionality.
Collapse
Affiliation(s)
| | - Hamed Tahmooressi
- Department of Mechanical Engineering, University of British Columbia, Kelowna, British Columbia V1V 1V7, Canada
| | - Hojatollah Rezaei Nejad
- Department of Electrical and Computer Engineering, Tufts University, 161 College Avenue, Medford, Massachusetts 02155, USA
| | | | - Su-Royn Shin
- Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02139, USA
- Authors to whom correspondence should be addressed: and
| | - Mina Hoorfar
- Faculty of Engineering, University of Victoria, Victoria, British Columbia V8W 2Y2, Canada
- Authors to whom correspondence should be addressed: and
| |
Collapse
|
|
36
|
Haseli M, Castilla-Casadiego DA, Pinzon-Herrera L, Hillsley A, Miranda-Munoz KA, Sivaraman S, Rosales AM, Rao RR, Almodovar J. Immunomodulatory functions of human mesenchymal stromal cells are enhanced when cultured on HEP/COL multilayers supplemented with interferon-gamma. Mater Today Bio 2022; 13:100194. [PMID: 35005599 PMCID: PMC8715375 DOI: 10.1016/j.mtbio.2021.100194] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/20/2021] [Accepted: 12/22/2021] [Indexed: 12/15/2022] Open
Abstract
Human mesenchymal stromal cells (hMSCs) are multipotent cells that have been proposed for cell therapies due to their immunosuppressive capacity that can be enhanced in the presence of interferon-gamma (IFN-γ). In this study, multilayers of heparin (HEP) and collagen (COL) (HEP/COL) were used as a bioactive surface to enhance the immunomodulatory activity of hMSCs using soluble IFN-γ. Multilayers were formed, via layer-by-layer assembly, varying the final layer between COL and HEP and supplemented with IFN-γ in the culture medium. We evaluated the viability, adhesion, real-time growth, differentiation, and immunomodulatory activity of hMSCs on (HEP/COL) multilayers. HMSCs viability, adhesion, and growth were superior when cultured on (HEP/COL) multilayers compared to tissue culture plastic. We also confirmed that hMSCs osteogenic and adipogenic differentiation remained unaffected when cultured in (HEP/COL) multilayers in the presence of IFN-γ. We measured the immunomodulatory activity of hMSCs by measuring the level of indoleamine 2,3-dioxygenase (IDO) expression. IDO expression was higher on (HEP/COL) multilayers treated with IFN-γ. Lastly, we evaluated the suppression of peripheral blood mononuclear cell (PBMC) proliferation when co-cultured with hMSCs on (HEP/COL) multilayers with IFN-γ. hMSCs cultured in (HEP/COL) multilayers in the presence of soluble IFN-γ have a greater capacity to suppress PBMC proliferation. Altogether, (HEP/COL) multilayers with IFN-γ in culture medium provides a potent means of enhancing and sustaining immunomodulatory activity to control hMSCs immunomodulation.
Collapse
Affiliation(s)
- Mahsa Haseli
- Ralph E. Martin Department of Chemical Engineering, University of Arkansas, 3202 Bell Engineering Center, Fayetteville, AR, 72701, USA
| | - David A. Castilla-Casadiego
- Ralph E. Martin Department of Chemical Engineering, University of Arkansas, 3202 Bell Engineering Center, Fayetteville, AR, 72701, USA
- Mcketta Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, 78712, USA
| | - Luis Pinzon-Herrera
- Ralph E. Martin Department of Chemical Engineering, University of Arkansas, 3202 Bell Engineering Center, Fayetteville, AR, 72701, USA
| | - Alexander Hillsley
- Mcketta Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, 78712, USA
| | - Katherine A. Miranda-Munoz
- Department of Biomedical Engineering, College of Engineering, University of Arkansas, Fayetteville, AR, 72701, USA
| | - Srikanth Sivaraman
- Department of Biomedical Engineering, College of Engineering, University of Arkansas, Fayetteville, AR, 72701, USA
| | - Adrianne M. Rosales
- Mcketta Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, 78712, USA
| | - Raj R. Rao
- Department of Biomedical Engineering, College of Engineering, University of Arkansas, Fayetteville, AR, 72701, USA
| | - Jorge Almodovar
- Ralph E. Martin Department of Chemical Engineering, University of Arkansas, 3202 Bell Engineering Center, Fayetteville, AR, 72701, USA
| |
Collapse
|
|
37
|
Combinations of Hydrogels and Mesenchymal Stromal Cells (MSCs) for Cartilage Tissue Engineering-A Review of the Literature. Gels 2021; 7:gels7040217. [PMID: 34842678 PMCID: PMC8628761 DOI: 10.3390/gels7040217] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 11/11/2021] [Accepted: 11/13/2021] [Indexed: 01/17/2023] Open
Abstract
Cartilage offers limited regenerative capacity. Cell-based approaches have emerged as a promising alternative in the treatment of cartilage defects and osteoarthritis. Due to their easy accessibility, abundancy, and chondrogenic potential mesenchymal stromal cells (MSCs) offer an attractive cell source. MSCs are often combined with natural or synthetic hydrogels providing tunable biocompatibility, biodegradability, and enhanced cell functionality. In this review, we focused on the different advantages and disadvantages of various natural, synthetic, and modified hydrogels. We examined the different combinations of MSC-subpopulations and hydrogels used for cartilage engineering in preclinical and clinical studies and reviewed the effects of added growth factors or gene transfer on chondrogenesis in MSC-laden hydrogels. The aim of this review is to add to the understanding of the disadvantages and advantages of various combinations of MSC-subpopulations, growth factors, gene transfers, and hydrogels in cartilage engineering.
Collapse
|
|
38
|
Huynh PD, Vu NB, To XHV, Le TM. Culture and Differentiation of Human Umbilical Cord-Derived Mesenchymal Stem Cells on Growth Factor-Rich Fibrin Scaffolds to Produce Engineered Cartilages. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021:193-208. [PMID: 34739721 DOI: 10.1007/5584_2021_670] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
INTRODUCTION After injuries, the cartilage healing capacity is limited owing to its nature as a particular connective tissue without blood vessels, lymphatics, or nerves. The creation of artificial cartilage tissue mimics the biological properties of native cartilage and can reduce the need for donated tissue. Fibrin is a type of biodegradable scaffold that has great potential in tissue engineering applications. It can become good material for cell adhesion and proliferation in vitro. Therefore, this study aimed to create a cartilage tissue in vitro using umbilical cord-derived mesenchymal stem cells (UCMSC) and growth factor-rich fibrin (GRF) scaffolds. METHODS UCMSCs were isolated and expanded, and platelet-rich plasma (PRP) preparations were performed following previously published protocols. PRP was activated (aPRP) by a 0.45-μm syringe filter to release growth factors inside the platelets. Each 2.105 of the UCMSCs were suspended in 2 ml of aPRP to make the mixture of MSC and PRP (MSC-PRP). Then, Ca2+ solution was added to this mixture to produce the fibril scaffold with UCMSCs inside. UCMSCs' adhesion and proliferation inside the scaffold were evaluated by observation under inverted microscopy, H-E staining, MTT assays, and scanning electron microscopy (SEM). The fibril structure containing UCMSCs was cultured, and chondrogenesis was induced using commercial chondrogenesis media for 21 days (iMSC-GRF). The differentiation in efficacy toward cartilage was evaluated based on the accumulation of aggrecan (acan), glycosaminoglycans (GAGs), and collagen type II (Col II). RESULTS The results showed that we successfully created a cartilage tissue with some characteristics that mimic the properties of natural cartilage. The engineered cartilage tissue was positive with some cartilage protein, such as acan, GAG, and Coll II. In vitro cartilage presented some natural chondrocyte-like cells. The artificial cartilage tissue was positive for CD14, CD34, CD90, CD105, and HLA-DR and negative for CD44, CD45, and CD73. CONCLUSION These results showed that using UCMSCs and growth factor-rich fibril from platelet-rich plasma was feasible to produce engineered cartilage tissue for further experiments or clinical usage.
Collapse
Affiliation(s)
- Phat Duc Huynh
- Laboratory of Stem Cell Research and Application, University of Science Ho Chi Minh City, Ho Chi Minh City, Vietnam
- Vietnam National University Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Ngoc Bich Vu
- Vietnam National University Ho Chi Minh City, Ho Chi Minh City, Vietnam.
- Stem Cell Institute, University of Science Ho Chi Minh City, Ho Chi Minh City, Vietnam.
| | - Xuan Hoang-Viet To
- Vietnam National University Ho Chi Minh City, Ho Chi Minh City, Vietnam
- Stem Cell Institute, University of Science Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Thuan Minh Le
- Laboratory of Stem Cell Research and Application, University of Science Ho Chi Minh City, Ho Chi Minh City, Vietnam
- Vietnam National University Ho Chi Minh City, Ho Chi Minh City, Vietnam
| |
Collapse
|
|
39
|
Bhalerao A, Raut S, Noorani B, Mancuso S, Cucullo L. Molecular Mechanisms of Multi-Organ Failure in COVID-19 and Potential of Stem Cell Therapy. Cells 2021; 10:2878. [PMID: 34831101 PMCID: PMC8616204 DOI: 10.3390/cells10112878] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 10/18/2021] [Accepted: 10/22/2021] [Indexed: 01/08/2023] Open
Abstract
As the number of confirmed cases and deaths occurring from Coronavirus disease 2019 (COVID-19) surges worldwide, health experts are striving hard to fully comprehend the extent of damage caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although COVID-19 primarily manifests itself in the form of severe respiratory distress, it is also known to cause systemic damage to almost all major organs and organ systems within the body. In this review, we discuss the molecular mechanisms leading to multi-organ failure seen in COVID-19 patients. We also examine the potential of stem cell therapy in treating COVID-19 multi-organ failure cases.
Collapse
Affiliation(s)
- Aditya Bhalerao
- Department of Biological and Biomedical Sciences, Oakland University, Rochester, MI 48309, USA
| | - Snehal Raut
- Department of Foundational Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USA
| | - Behnam Noorani
- Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA
| | - Salvatore Mancuso
- Department of Biological and Biomedical Sciences, Oakland University, Rochester, MI 48309, USA
| | - Luca Cucullo
- Department of Foundational Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USA
| |
Collapse
|
|
40
|
Mollah MZI, Zahid HM, Mahal Z, Faruque MRI, Khandaker MU. The Usages and Potential Uses of Alginate for Healthcare Applications. Front Mol Biosci 2021; 8:719972. [PMID: 34692769 PMCID: PMC8530156 DOI: 10.3389/fmolb.2021.719972] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 09/07/2021] [Indexed: 01/09/2023] Open
Abstract
Due to their unique properties, alginate-based biomaterials have been extensively used to treat different diseases, and in the regeneration of diverse organs. A lot of research has been done by the different scientific community to develop biofilms for fulfilling the need for sustainable human health. The aim of this review is to hit upon a hydrogel enhancing the scope of utilization in biomedical applications. The presence of active sites in alginate hydrogels can be manipulated for managing various non-communicable diseases by encapsulating, with the bioactive component as a potential site for chemicals in developing drugs, or for delivering macromolecule nutrients. Gels are accepted for cell implantation in tissue regeneration, as they can transfer cells to the intended site. Thus, this review will accelerate advanced research avenues in tissue engineering and the potential of alginate biofilms in the healthcare sector.
Collapse
Affiliation(s)
- M. Z. I. Mollah
- Space Science Centre (ANGKASA), Universiti Kebangsaan Malaysia, Bangi, Malaysia
- Institute of Radiation and Polymer Technology, Bangladesh Atomic Energy Commission, Dhaka, Bangladesh
| | - H. M. Zahid
- Institute of Radiation and Polymer Technology, Bangladesh Atomic Energy Commission, Dhaka, Bangladesh
| | - Z. Mahal
- Institute of Radiation and Polymer Technology, Bangladesh Atomic Energy Commission, Dhaka, Bangladesh
| | | | - M. U. Khandaker
- Centre for Applied Physics and Radiation Technologies, School of Engineering and Technology, Sunway University, Selangor, Malaysia
| |
Collapse
|
|
41
|
Functional heterogeneity of IFN-γ-licensed mesenchymal stromal cell immunosuppressive capacity on biomaterials. Proc Natl Acad Sci U S A 2021; 118:2105972118. [PMID: 34446555 DOI: 10.1073/pnas.2105972118] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Mesenchymal stromal cells (MSCs) are increasingly combined with biomaterials to enhance their therapeutic properties, including their immunosuppressive function. However, clinical trials utilizing MSCs with or without biomaterials have shown limited success, potentially due to their functional heterogeneity across different donors and among different subpopulations of cells. Here, we evaluated the immunosuppressive capacity, as measured by the ability to reduce T-cell proliferation and activation, of interferon-gamma (IFN-γ)-licensed MSCs from multiple donors on fibrin and collagen hydrogels, the two most commonly utilized biomaterials in combination with MSCs in clinical trials worldwide according to ClinicalTrials.gov Variations in the immunosuppressive capacity between IFN-γ-licensed MSC donors on the biomaterials correlated with the magnitude of indoleamine-2,3-dioxygenase activity. Immunosuppressive capacity of the IFN-γ-licensed MSCs depended on the αV/α5 integrins when cultured on fibrin and on the α2/β1 integrins when cultured on collagen. While all tested MSCs were nearly 100% positive for these integrins, sorted MSCs that expressed higher levels of αV/α5 integrins demonstrated greater immunosuppressive capacity with IFN-γ licensing than MSCs that expressed lower levels of these integrins on fibrin. These findings were equivalent for MSCs sorted based on the α2/β1 integrins on collagen. These results demonstrate the importance of integrin engagement to IFN-γ licensed MSC immunosuppressive capacity and that IFN-γ-licensed MSC subpopulations of varying immunosuppressive capacity can be identified by the magnitude of integrin expression specific to each biomaterial.
Collapse
|
|
42
|
Oral Cavity as a Source of Mesenchymal Stem Cells Useful for Regenerative Medicine in Dentistry. Biomedicines 2021; 9:biomedicines9091085. [PMID: 34572271 PMCID: PMC8469189 DOI: 10.3390/biomedicines9091085] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 08/19/2021] [Accepted: 08/23/2021] [Indexed: 12/17/2022] Open
Abstract
The use of mesenchymal stem cells (MSCs) for regenerative purposes has become common in a large variety of diseases. In the dental and maxillofacial field, there are emerging clinical needs that could benefit from MSC-based therapeutic approaches. Even though MSCs can be isolated from different tissues, such as bone marrow, adipose tissue, etc., and are known for their multilineage differentiation, their different anatomical origin can affect the capability to differentiate into a specific tissue. For instance, MSCs isolated from the oral cavity might be more effective than adipose-derived stem cells (ASCs) for the treatment of dental defects. Indeed, in the oral cavity, there are different sources of MSCs that have been individually proposed as promising candidates for tissue engineering protocols. The therapeutic strategy based on MSCs can be direct, by using cells as components of the tissue to be regenerated, or indirect, aimed at delivering local growth factors, cytokines, and chemokines produced by the MSCs. Here, the authors outline the major sources of mesenchymal stem cells attainable from the oral cavity and discuss their possible usage in some of the most compelling therapeutic frontiers, such as periodontal disease and dental pulp regeneration.
Collapse
|
|
43
|
Miri V, Asadi A, Sagha M, Najafzadeh N, Golmohammadi MG. Poly (L-lactic acid) nanofibrous scaffolds support the proliferation and neural differentiation of mouse neural stem and progenitor cells. Int J Dev Neurosci 2021; 81:438-447. [PMID: 33934403 DOI: 10.1002/jdn.10119] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 04/28/2021] [Accepted: 04/28/2021] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND The distribution and growth of cells on nanofibrous scaffolds seem to be an indispensable precondition in cell tissue engineering. The potential use of biomaterial scaffolds in neural stem cell therapy is increasingly attracting attention. AIM In this study, we produced porous nanofibrous scaffolds fabricated from random poly-L-lactic acid (PLLA) to support neurogenic differentiation of neural stem and progenitor cells (NSPCs), isolated from the subventricular zone (SVZ) of the adult mouse brain. METHODS The viability and proliferation of the NSPCs on the nanofibrous PLLA scaffold were also tested by nuclear staining with 4, 6-diamidino-2-phenylindole dihydrochloride (DAPI), 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and scanning electron microscopy (SEM). To investigate the differentiation potential of NSPCs on the scaffolds, the cells were treated with a neurogenic differentiation medium, and immunostaining was done to detect neuronal and glial cells after 14 and 21 days of cultivation. Furthermore, the morphology of differentiated cells on the scaffold was examined using SEM. RESULTS The DAPI staining revealed the proliferation of NSPCs onto the surface of the nanofibrous PLLA scaffold. DAPI-positive cells were counted on days 2 and 5 after cultivation. The mean number of cells in each microscopic field was significantly (p < .05) increased (51 ± 19 on day 2 compared to 77 ± 25 cells on day 5). The results showed that the cell viability on PLLA scaffolds significantly increased compared to control groups. Moreover, cell viability was significantly increased 5 days after culturing (262.3 ± 50.2) as compared to 2 days culture in Vitro (174.2 ± 28.3, p < .05). Scanning electron micrographs also showed that the NSPCs adhered and differentiated on PLLA scaffolds. We found that the neural cell markers, microtubule-associated protein 2 (MAP2) and glial fibrillary acidic protein (GFAP), were expressed in NSPCs seeded on random PLLA scaffolds after 21 days of cultivation. CONCLUSION These results suggest that the PLLA nano-scaffolds, due to their biocompatible property, are an appropriate structure for the proliferation, differentiation, and normal growth of NSPCs.
Collapse
Affiliation(s)
- Vahideh Miri
- Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran
- Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Asadollah Asadi
- Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Mohsen Sagha
- Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Nowruz Najafzadeh
- Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Mohammad Ghasem Golmohammadi
- Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| |
Collapse
|
|
44
|
Lee NH, Na SM, Ahn HW, Kang JK, Seon JK, Song EK. Allogenic Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Are More Effective Than Bone Marrow Aspiration Concentrate for Cartilage Regeneration After High Tibial Osteotomy in Medial Unicompartmental Osteoarthritis of Knee. Arthroscopy 2021; 37:2521-2530. [PMID: 33621649 DOI: 10.1016/j.arthro.2021.02.022] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 02/08/2021] [Accepted: 02/11/2021] [Indexed: 02/02/2023]
Abstract
PURPOSE The purpose of this study was to compare the outcome of cartilage regeneration between bone marrow aspirate concentrate (BMAC) augmentation and allogeneic human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSCs) transplantation in high tibial osteotomy (HTO) with microfracture (MFX) for medial unicompartmental osteoarthritis (OA) of the knee in the young and active patient. METHODS Between January 2015 and December 2019, the patients who underwent HTO and arthroscopy with MFX combined with BMAC or allogeneic hUCB-MSCs procedure for medial unicompartmental OA with kissing lesion, which was shown full-thickness cartilage defect (≥ International Cartilage Repair Society [ICRS] grade 3B) in medial femoral cartilage and medial tibial cartilage, were include in this study. Retrospectively we compared clinical outcomes, including Hospital for Special Surgery score, Knee Society Score (KSS) pain and function, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score between BMAC and hUCB-MSCs group at minimum of 1-year follow-up. Also, second-look arthroscopy was performed simultaneously with removal of the plate after complete bone union. Cartilage regeneration was graded by the ICRS grading system at second-look arthroscopy. Radiological measurement including hip-knee-ankle (HKA) angle, posterior tibial slope angle, and correction angle were assessed. RESULTS Of 150 cases that underwent HTO with MFX combined with BMAC or allogeneic hUCB-MSCs procedure for medial unicompartmental OA, 123 cases underwent plate removal and second-look arthroscopy after a minimum of 1 year after the HTO surgery. Seventy-four cases were kissing lesion in medial femoral cartilage and medial tibial cartilage during initial HTO surgery. Finally, the BMAC group composed of 42 cases and hUCB-MSCs group composed of 32 cases were retrospectively identified in patients who had kissing lesions and second-look arthroscopies with a minimum of 1 year of follow-up. At the final follow-up of mean 18.7 months (standard deviation = 4.6 months), clinical outcomes in both groups had improved. However, there were no significant differences between the IKDC, WOMAC, or KSS pain and function scores in the 2 groups (P > .05). At second-look arthroscopy, the ICRS grade was significantly better in the hUCB-MSC group than in the BMAC group in both medial femoral and medial tibial cartilage (P = .001 for both). The average ICRS grade of the BMAC group improved from 3.9 before surgery to 2.8 after surgery. The average ICRS grade of the hUBC-MSC group improved from 3.9 before surgery to 2.0 after surgery. Radiological findings comparing postoperative HKA angle, posterior tibial slope angle, and correction angle showed no significant differences between the groups (P > .05). Therefore it was found that the postoperative correction amount did not affect the postoperative cartilage regeneration results. CONCLUSIONS We found that the hUCB-MSC procedure was more effective than the BMAC procedure for cartilage regeneration in medial unicompartmental knee OA even though the clinical outcomes improved regardless of which treatment was administered. LEVEL OF EVIDENCE Level III, retrospective comparative study.
Collapse
Affiliation(s)
- Nam-Hun Lee
- Department of Orthopaedic Surgery, Chonnam National University Medical School and Hospital, Hwasun, Republic of Korea
| | - Seung-Min Na
- Department of Orthopaedic Surgery, Chonnam National University Medical School and Hospital, Hwasun, Republic of Korea
| | - Hyeon-Wook Ahn
- Department of Orthopaedic Surgery, Chonnam National University Medical School and Hospital, Hwasun, Republic of Korea
| | - Joon-Kyoo Kang
- Department of Orthopaedic Surgery, Chonnam National University Medical School and Hospital, Hwasun, Republic of Korea
| | - Jong-Keun Seon
- Department of Orthopaedic Surgery, Chonnam National University Medical School and Hospital, Hwasun, Republic of Korea.
| | - Eun-Kyoo Song
- Department of Orthopaedic Surgery, Chonnam National University Medical School and Hospital, Hwasun, Republic of Korea
| |
Collapse
|
|
45
|
Sternal Bone Marrow Harvesting and Culturing Techniques from Patients Undergoing Cardiac Surgery. MICROMACHINES 2021; 12:mi12080897. [PMID: 34442518 PMCID: PMC8397946 DOI: 10.3390/mi12080897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 07/24/2021] [Accepted: 07/26/2021] [Indexed: 11/17/2022]
Abstract
Background: Mesenchymal stromal cells (MSCs) are the most prominent cell type used in clinical regenerative medicine and stem cell research. MSCs are commonly harvested from bone marrow that has been aspirated from patients’ iliac crest. However, the ethical challenges of finding consenting patients and obtaining fresh autologous cells via invasive extraction methods remain to be barriers to MSC research. Methods: Techniques of harvesting sternal bone marrow, isolating and culturing MSCs, MSC surface phenotyping, and MSC differentiation are described. Samples from 50 patients undergoing a sternotomy were collected, and the time taken to reach 80% confluency and cell count at the second splitting of MSC were measured. Results: MSC isolated from the sternal bone marrow of patients undergoing cardiac surgery demonstrated successful MSC surface phenotyping and MSC differentiation. The mean cell count at the time of the second split was 1,628,025, and the mean time taken to reach the second split was 24.8 days. Conclusion: Herein, we describe the first reported technique of harvesting sternal bone marrow from patients already undergoing open-chest cardiac surgery to reduce the invasiveness of bone marrow harvesting, as well as the methods of isolating, culturing, and identifying MSCs for the clinical application of constructing autologous MSC-derived biomaterials.
Collapse
|
|
46
|
Xu Y, Zhang WX, Wang LN, Ming YQ, Li YL, Ni GX. Stem cell therapies in tendon-bone healing. World J Stem Cells 2021; 13:753-775. [PMID: 34367476 PMCID: PMC8316867 DOI: 10.4252/wjsc.v13.i7.753] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 05/08/2021] [Accepted: 06/23/2021] [Indexed: 02/06/2023] Open
Abstract
Tendon-bone insertion injuries such as rotator cuff and anterior cruciate ligament injuries are currently highly common and severe. The key method of treating this kind of injury is the reconstruction operation. The success of this reconstructive process depends on the ability of the graft to incorporate into the bone. Recently, there has been substantial discussion about how to enhance the integration of tendon and bone through biological methods. Stem cells like bone marrow mesenchymal stem cells (MSCs), tendon stem/progenitor cells, synovium-derived MSCs, adipose-derived stem cells, or periosteum-derived periosteal stem cells can self-regenerate and potentially differentiate into different cell types, which have been widely used in tissue repair and regeneration. Thus, we concentrate in this review on the current circumstances of tendon-bone healing using stem cell therapy.
Collapse
Affiliation(s)
- Yue Xu
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Wan-Xia Zhang
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Li-Na Wang
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Yue-Qing Ming
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Yu-Lin Li
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Guo-Xin Ni
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China.
| |
Collapse
|
|
47
|
Roudsari PP, Alavi-Moghadam S, Rezaei-Tavirani M, Goodarzi P, Tayanloo-Beik A, Sayahpour FA, Larijani B, Arjmand B. The Outcome of Stem Cell-Based Therapies on the Immune Responses in Rheumatoid Arthritis. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1326:159-186. [PMID: 32926346 DOI: 10.1007/5584_2020_581] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/12/2023]
Abstract
Rheumatoid arthritis as a common autoimmune inflammatory disorder with unknown etiology can affect 0.5-1% of adults in developed countries. It involves more than just the patient's joints and can be accompanied by several comorbidities and affect cardiovascular, pulmonary, and some other systems of the human body. Although cytokine-mediated pathways are mentioned to have a central role in RA pathogenesis, adaptive and innate immune systems and intracellular signaling pathways all have important roles in this process. Non-steroidal anti-inflammatory drugs, glucocorticoids, conventional disease-modifying anti-rheumatic drugs, and biological agents are some mentioned medications used for RA. They are accompanied by some adverse effects and treatment failures which elucidates the needing for novel and more powerful therapeutic approaches. Stem cell-based therapies and their beneficial effects on therapeutic processes of different diseases have been founded so far. They can be an alternative and promising therapeutic approach for RA, too; due to their effects on immune responses of the disease. This review, besides some explanations about RA characteristics, addresses the outcome of the stem cell-based therapies including mesenchymal stem cell transplantation and hematopoietic stem cell transplantation for RA and explains their effects on the disease improvement.
Collapse
Affiliation(s)
- Peyvand Parhizkar Roudsari
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sepideh Alavi-Moghadam
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Parisa Goodarzi
- Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Akram Tayanloo-Beik
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Forough Azam Sayahpour
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical sciences, Tehran, Iran
| | - Babak Arjmand
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. .,Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
48
|
Ge Y, Li Y, Wang Z, Li L, Teng H, Jiang Q. Effects of Mechanical Compression on Chondrogenesis of Human Synovium-Derived Mesenchymal Stem Cells in Agarose Hydrogel. Front Bioeng Biotechnol 2021; 9:697281. [PMID: 34350163 PMCID: PMC8327094 DOI: 10.3389/fbioe.2021.697281] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 06/22/2021] [Indexed: 01/22/2023] Open
Abstract
Mechanical compression is a double-edged sword for cartilage remodeling, and the effect of mechanical compression on chondrogenic differentiation still remains elusive to date. Herein, we investigate the effect of mechanical dynamic compression on the chondrogenic differentiation of human synovium-derived mesenchymal stem cells (SMSCs). To this aim, SMSCs encapsulated in agarose hydrogels were cultured in chondrogenic-induced medium with or without dynamic compression. Dynamic compression was applied at either early time-point (day 1) or late time-point (day 21) during chondrogenic induction period. We found that dynamic compression initiated at early time-point downregulated the expression level of chondrocyte-specific markers as well as hypertrophy-specific markers compared with unloaded control. On the contrary, dynamic compression applied at late time-point not only enhanced the levels of cartilage matrix gene expression, but also suppressed the hypertrophic development of SMSCs compared with unloaded controls. Taken together, our findings suggest that dynamic mechanical compression loading not only promotes chondrogenic differentiation of SMSCs, but also plays a vital role in the maintenance of cartilage phenotype, and our findings also provide an experimental guide for stem cell-based cartilage repair and regeneration.
Collapse
Affiliation(s)
- Yuxiang Ge
- State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.,Laboratory for Bone and Joint Disease, Model Animal Research Center, Nanjing University, Nanjing, China
| | - Yixuan Li
- State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.,Laboratory for Bone and Joint Disease, Model Animal Research Center, Nanjing University, Nanjing, China
| | - Zixu Wang
- State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.,Laboratory for Bone and Joint Disease, Model Animal Research Center, Nanjing University, Nanjing, China
| | - Lan Li
- State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.,Jiangsu Engineering Research Center for 3D Bioprinting, Nanjing, China
| | - Huajian Teng
- Laboratory for Bone and Joint Disease, Model Animal Research Center, Nanjing University, Nanjing, China
| | - Qing Jiang
- State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.,Laboratory for Bone and Joint Disease, Model Animal Research Center, Nanjing University, Nanjing, China
| |
Collapse
|
|
49
|
Huang Y, Liao L, Su H, Chen X, Jiang T, Liu J, Hou Q. Psoralen accelerates osteogenic differentiation of human bone marrow mesenchymal stem cells by activating the TGF-β/Smad3 pathway. Exp Ther Med 2021; 22:940. [PMID: 34306204 PMCID: PMC8281312 DOI: 10.3892/etm.2021.10372] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 05/07/2021] [Indexed: 12/18/2022] Open
Abstract
Psoralen, one of the active ingredients in Psoralea corylifolia, has been previously reported to regulate the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). A previous study revealed that psoralen can regulate the expression levels of microRNA-488 and runt-related transcription factor 2 (Runx2) to promote the osteogenic differentiation of BMSCs. However, the underlying signalling pathway in this process remains to be fully elucidated. BMSCs have also been confirmed to play a key role in the occurrence and development of osteoporosis, and are expected to be potential seed cells in the treatment of osteoporosis. In order to explore the potential signalling pathways of psoralen acting on BMSCs, in the present study, human BMSCs (hBMSCs) were treated with different concentrations of psoralen (0.1, 1, 10 and 100 µmol/l) and the TGF-β receptor I (RI) inhibitor SB431542 (5 µmol/l) in vitro for 3, 7 or 14 days. Cell Counting Kit-8 and MTT assays were used to measure cell proliferation and cell viability of hBMSCs following psoralen administration. Alkaline phosphatase (ALP) activity and alizarin red S staining were used to assess the osteogenic differentiation ability of hBMSCs. Reverse transcription-quantitative PCR and western blotting were used to measure the expression of osteogenic differentiation-related genes [bone morphogenetic protein 4 (BMP4), osteopontin (OPN), Runx2 and Osterix] and proteins associated with the TGF-β/Smad3 pathway [TGF-β1, TGF-β RI, phosphorylated (p-)Smad and Smad3]. Psoralen was found to increase the proliferation and viability of hBMSCs. Although different concentrations of psoralen enhanced ALP activity and the calcified nodule content in hBMSCs, the enhancement effects were more potent at lower concentrations (0.1, 1 and 10 µmol/l). The expression of BMP4, OPN, Osterix, Runx2, TGF-β1, TGF-β RI and p-Smad3 was also promoted by psoralen at lower concentrations (0.1, 1 and 10 µmol/l). In addition, whilst SB431542 could inhibit calcium deposition and osteogenic differentiation-related gene expression in hBMSCs, psoralen effectively reversed the inhibitory effects of SB431542. In conclusion, psoralen accelerates the osteogenic differentiation of hBMSCs by activating the TGF-β/Smad3 pathway, which may be valuable for the future clinical treatment of osteoporosis.
Collapse
Affiliation(s)
- Yongquan Huang
- Department of Orthopaedics, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China.,Graduate School, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Liu Liao
- Graduate School, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Haitao Su
- Department of Orthopaedics, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China
| | - Xinlin Chen
- Department of Preventive Medicine and Health Statistics, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Tao Jiang
- Department of Orthopaedics, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China
| | - Jun Liu
- Department of Orthopaedics, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China
| | - Qiuke Hou
- Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| |
Collapse
|
|
50
|
Ren Y, Yang X, Ma Z, Sun X, Zhang Y, Li W, Yang H, Qiang L, Yang Z, Liu Y, Deng C, Zhou L, Wang T, Lin J, Li T, Wu T, Wang J. Developments and Opportunities for 3D Bioprinted Organoids. Int J Bioprint 2021; 7:364. [PMID: 34286150 PMCID: PMC8287496 DOI: 10.18063/ijb.v7i3.364] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Accepted: 05/08/2021] [Indexed: 12/11/2022] Open
Abstract
Organoids developed from pluripotent stem cells or adult stem cells are three-dimensional cell cultures possessing certain key characteristics of their organ counterparts, and they can mimic certain biological developmental processes of organs in vitro. Therefore, they have promising applications in drug screening, disease modeling, and regenerative repair of tissues and organs. However, the construction of organoids currently faces numerous challenges, such as breakthroughs in scale size, vascularization, better reproducibility, and precise architecture in time and space. Recently, the application of bioprinting has accelerated the process of organoid construction. In this review, we present current bioprinting techniques and the application of bioinks and summarize examples of successful organoid bioprinting. In the future, a multidisciplinary combination of developmental biology, disease pathology, cell biology, and materials science will aid in overcoming the obstacles pertaining to the bioprinting of organoids. The combination of bioprinting and organoids with a focus on structure and function can facilitate further development of real organs.
Collapse
Affiliation(s)
- Ya Ren
- Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Rd, Shanghai 200011, China
- Southwest JiaoTong University College of Medicine, No. 111 North 1 Section of Second Ring Road, Chengdu 610036, China
| | - Xue Yang
- Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Rd, Shanghai 200011, China
- Southwest JiaoTong University College of Medicine, No. 111 North 1 Section of Second Ring Road, Chengdu 610036, China
| | - Zhengjiang Ma
- Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Rd, Shanghai 200011, China
| | - Xin Sun
- Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Rd, Shanghai 200011, China
| | - Yuxin Zhang
- Department of Rehabilitation Medicine, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Huangpu District, Shanghai 200011, China
| | - Wentao Li
- Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Rd, Shanghai 200011, China
| | - Han Yang
- Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Rd, Shanghai 200030, China
| | - Lei Qiang
- Key Laboratory of Advanced Technology of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610036, China
| | - Zezheng Yang
- Department of Orthopedics, The Fifth People’s Hospital of Shanghai, Fudan University, Minhang District, Shanghai 200240, P. R. China
| | - Yihao Liu
- Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Rd, Shanghai 200011, China
| | - Changxu Deng
- Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Rd, Shanghai 200011, China
| | - Liang Zhou
- Center for Medicine Intelligent and Development, China Hospital Development Institute, Shanghai Jiao Tong University, Shanghai 200020, China
| | - Tianchang Wang
- Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Rd, Shanghai 200011, China
| | - Jingsheng Lin
- Department of Information Technology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Tao Li
- Department of Orthopaedics, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P. R. China
| | - Tao Wu
- Shanghai University of Medicine and Health Sciences, Shanghai 200120, China
| | - Jinwu Wang
- Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Rd, Shanghai 200011, China
- Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Rd, Shanghai 200030, China
| |
Collapse
|