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Peng Q, Qian Y, Xiao X, Gao F, Ren G, Pennisi CP. Advancing Chronic Wound Healing through Electrical Stimulation and Adipose-Derived Stem Cells. Adv Healthc Mater 2025; 14:e2403777. [PMID: 40025921 PMCID: PMC12004429 DOI: 10.1002/adhm.202403777] [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: 10/01/2024] [Revised: 01/24/2025] [Indexed: 03/04/2025]
Abstract
Chronic cutaneous wounds are a major clinical challenge worldwide due to delayed healing, recurrent infections, and resistance to conventional therapies. Adipose-derived stem cells (ASCs) have shown promise as a cell-based therapy, but their therapeutic efficacy is often compromised by the harsh microenvironment of chronic wounds. Recent advances in bioengineering, particularly the application of electrical stimulation (ES), offer an innovative approach to enhancing the regenerative properties of ASCs. By restoring the natural electrical current in the wound, ES provides a strong stimulus to the cells involved in healing, thereby accelerating the overall wound-healing process. Recent studies show that ASCs can be significantly activated by ES, which increases their viability, proliferation, migration, and secretory capacity, all of which are crucial for the proper healing of chronic wounds. This review examines the synergistic effects of ES and ASCs on wound healing, focusing on the biological mechanisms involved. The review also highlights novel self-powered systems and other emerging technologies such as advanced conductive materials and devices that promise to improve the clinical translation of ES-based treatments. By summarizing the current state of knowledge, this review aims to provide a framework for future research and clinical application of ES and ASCs in wound care.
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Affiliation(s)
- Qiuyue Peng
- Department of Health Science and TechnologyAalborg UniversityGistrup9260Denmark
| | - Yu Qian
- Department of Health Science and TechnologyAalborg UniversityGistrup9260Denmark
| | - Xinxin Xiao
- Department of Chemistry and BioscienceAalborg UniversityGistrup9260Denmark
| | - Fengdi Gao
- Department of Health Science and TechnologyAalborg UniversityGistrup9260Denmark
| | - Guoqiang Ren
- The Affiliated Lihuili Hospital of Ningbo University, Department of DermatologyNingbo315046China
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Gu C, Tang Q, Li L, Chen Y. Optimization and Implication of Adipose-Derived Stem Cells in Craniofacial Bone Regeneration and Repair. Bioengineering (Basel) 2024; 11:1100. [PMID: 39593759 PMCID: PMC11592193 DOI: 10.3390/bioengineering11111100] [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: 09/14/2024] [Revised: 10/17/2024] [Accepted: 10/27/2024] [Indexed: 11/28/2024] Open
Abstract
Adipose-derived stem cells (ADSCs) have emerged as a promising resource for craniofacial bone regeneration due to their high abundance and easy accessibility, significant osteogenic potential, versatile applications, and potential for personalized medicine, which underscore their importance in this field. This article reviews the current progress of preclinical studies that describe the careful selection of specific ADSC subpopulations, key signaling pathways involved, and usage of various strategies to enhance the osteogenic potential of ADSCs. Additionally, clinical case reports regarding the application of ADSCs in the repair of calvarial defects, cranio-maxillofacial defects, and alveolar bone defects are also discussed.
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Affiliation(s)
- Cong Gu
- Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA; (Q.T.); (L.L.); (Y.C.)
| | - Qinghuang Tang
- Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA; (Q.T.); (L.L.); (Y.C.)
- Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY 14214, USA
| | - Liwen Li
- Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA; (Q.T.); (L.L.); (Y.C.)
- Department of Biological Sciences, University at Buffalo, Buffalo, NY 14260, USA
| | - YiPing Chen
- Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA; (Q.T.); (L.L.); (Y.C.)
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Preetam S, Ghosh A, Mishra R, Pandey A, Roy DS, Rustagi S, Malik S. Electrical stimulation: a novel therapeutic strategy to heal biological wounds. RSC Adv 2024; 14:32142-32173. [PMID: 39399261 PMCID: PMC11467653 DOI: 10.1039/d4ra04258a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 09/02/2024] [Indexed: 10/15/2024] Open
Abstract
Electrical stimulation (ES) has emerged as a powerful therapeutic modality for enhancing biological wound healing. This non-invasive technique utilizes low-level electrical currents to promote tissue regeneration and expedite the wound healing process. ES has been shown to accelerate wound closure, reduce inflammation, enhance angiogenesis, and modulate cell migration and proliferation through various mechanisms. The principle goal of wound management is the rapid recovery of the anatomical continuity of the skin, to prevent infections from the external environment and maintain homeostasis conditions inside. ES at the wound site is a compelling strategy for skin wound repair. Several ES applications are described in medical literature like AC, DC, and PC to improve cutaneous perfusion and accelerate wound healing. This review aimed to evaluate the primary factors and provides an overview of the potential benefits and mechanisms of ES in wound healing, and its ability to stimulate cellular responses, promote tissue regeneration, and improve overall healing outcomes. We also shed light on the application of ES which holds excellent promise as an adjunct therapy for various types of wounds, including chronic wounds, diabetic ulcers, and surgical incisions.
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Affiliation(s)
- Subham Preetam
- Department of Robotics and Mechatronics Engineering, Daegu Gyeongbuk Institute of Science and Technology (DGIST) Daegu 42988 Republic of Korea
| | - Arka Ghosh
- KIIT School of Biotechnology, Kalinga Institute of Industrial Technology Bhubaneswar 751003 Odisha India
| | - Richa Mishra
- Department of Computer Engineering, Parul Institute of Engineering and Technology (PIET), Parul University Ta. Waghodia Vadodara Gujarat 391760 India
| | - Arunima Pandey
- KIIT School of Biotechnology, Kalinga Institute of Industrial Technology Bhubaneswar 751003 Odisha India
| | - Debanjan Singha Roy
- KIIT School of Biotechnology, Kalinga Institute of Industrial Technology Bhubaneswar 751003 Odisha India
| | - Sarvesh Rustagi
- School of Applied and Life Sciences, Uttaranchal University 22 Dehradun Uttarakhand India
| | - Sumira Malik
- Amity Institute of Biotechnology, Amity University Jharkhand Ranchi Jharkhand 834001 India
- Department of Biotechnology, University Center for Research & Development (UCRD) Chandigarh University Ludhiana Highway Mohali 140413 Punjab India
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Chen J, Hao Z, Li H, Wang J, Chen T, Wang Y, Shi G, Wang J, Wang Z, Zhang Z, Li J. Osteoporotic osseointegration: therapeutic hallmarks and engineering strategies. Theranostics 2024; 14:3859-3899. [PMID: 38994021 PMCID: PMC11234277 DOI: 10.7150/thno.96516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 06/05/2024] [Indexed: 07/13/2024] Open
Abstract
Osteoporosis is a systemic skeletal disease caused by an imbalance between bone resorption and formation. Current treatments primarily involve systemic medication and hormone therapy. However, these systemic treatments lack directionality and are often ineffective for locally severe osteoporosis, with the potential for complex adverse reactions. Consequently, treatment strategies using bioactive materials or external interventions have emerged as the most promising approaches. This review proposes twelve microenvironmental treatment targets for osteoporosis-related pathological changes, including local accumulation of inflammatory factors and reactive oxygen species (ROS), imbalance of mitochondrial dynamics, insulin resistance, disruption of bone cell autophagy, imbalance of bone cell apoptosis, changes in neural secretions, aging of bone cells, increased local bone tissue vascular destruction, and decreased regeneration. Additionally, this review examines the current research status of effective or potential biophysical and biochemical stimuli based on these microenvironmental treatment targets and summarizes the advantages and optimal parameters of different bioengineering stimuli to support preclinical and clinical research on osteoporosis treatment and bone regeneration. Finally, the review addresses ongoing challenges and future research prospects.
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Affiliation(s)
- Jiayao Chen
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R. China
| | - Zhuowen Hao
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R. China
| | - Hanke Li
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R. China
| | - Jianping Wang
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R. China
| | - Tianhong Chen
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R. China
| | - Ying Wang
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China
| | - Guang Shi
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R. China
| | - Junwu Wang
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R. China
| | - Zepu Wang
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R. China
| | - Zheyuan Zhang
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R. China
| | - Jingfeng Li
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R. China
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Lin JJ, Ning T, Jia SC, Li KJ, Huang YC, Liu Q, Lin JH, Zhang XT. Evaluation of genetic response of mesenchymal stem cells to nanosecond pulsed electric fields by whole transcriptome sequencing. World J Stem Cells 2024; 16:305-323. [PMID: 38577234 PMCID: PMC10989289 DOI: 10.4252/wjsc.v16.i3.305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 01/31/2024] [Accepted: 02/28/2024] [Indexed: 03/25/2024] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSCs) modulated by various exogenous signals have been applied extensively in regenerative medicine research. Notably, nanosecond pulsed electric fields (nsPEFs), characterized by short duration and high strength, significantly influence cell phenotypes and regulate MSCs differentiation via multiple pathways. Consequently, we used transcriptomics to study changes in messenger RNA (mRNA), long noncoding RNA (lncRNA), microRNA (miRNA), and circular RNA expression during nsPEFs application. AIM To explore gene expression profiles and potential transcriptional regulatory mechanisms in MSCs pretreated with nsPEFs. METHODS The impact of nsPEFs on the MSCs transcriptome was investigated through whole transcriptome sequencing. MSCs were pretreated with 5-pulse nsPEFs (100 ns at 10 kV/cm, 1 Hz), followed by total RNA isolation. Each transcript was normalized by fragments per kilobase per million. Fold change and difference significance were applied to screen the differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to elucidate gene functions, complemented by quantitative polymerase chain reaction verification. RESULTS In total, 263 DEGs were discovered, with 92 upregulated and 171 downregulated. DEGs were predominantly enriched in epithelial cell proliferation, osteoblast differentiation, mesenchymal cell differentiation, nuclear division, and wound healing. Regarding cellular components, DEGs are primarily involved in condensed chromosome, chromosomal region, actin cytoskeleton, and kinetochore. From aspect of molecular functions, DEGs are mainly involved in glycosaminoglycan binding, integrin binding, nuclear steroid receptor activity, cytoskeletal motor activity, and steroid binding. Quantitative real-time polymerase chain reaction confirmed targeted transcript regulation. CONCLUSION Our systematic investigation of the wide-ranging transcriptional pattern modulated by nsPEFs revealed the differential expression of 263 mRNAs, 2 miRNAs, and 65 lncRNAs. Our study demonstrates that nsPEFs may affect stem cells through several signaling pathways, which are involved in vesicular transport, calcium ion transport, cytoskeleton, and cell differentiation.
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Affiliation(s)
- Jian-Jing Lin
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
| | - Tong Ning
- Institute of Medical Science, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, Shandong Province, China
| | - Shi-Cheng Jia
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
| | - Ke-Jia Li
- Department of Biomedical Engineering, Institute of Future Technology, Peking University, Beijing 100871, China
| | - Yong-Can Huang
- Shenzhen Engineering Laboratory of Orthopaedic Regenerative Technologies, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
| | - Qiang Liu
- Arthritis Clinical and Research Center, Peking University People's Hospital, Beijing 100044, China
| | - Jian-Hao Lin
- Arthritis Clinical and Research Center, Peking University People's Hospital, Beijing 100044, China
| | - Xin-Tao Zhang
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China.
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Omer SA, McKnight KH, Young LI, Song S. Stimulation strategies for electrical and magnetic modulation of cells and tissues. CELL REGENERATION (LONDON, ENGLAND) 2023; 12:21. [PMID: 37391680 DOI: 10.1186/s13619-023-00165-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Accepted: 05/01/2023] [Indexed: 07/02/2023]
Abstract
Electrical phenomena play an important role in numerous biological processes including cellular signaling, early embryogenesis, tissue repair and remodeling, and growth of organisms. Electrical and magnetic effects have been studied on a variety of stimulation strategies and cell types regarding cellular functions and disease treatments. In this review, we discuss recent advances in using three different stimulation strategies, namely electrical stimulation via conductive and piezoelectric materials as well as magnetic stimulation via magnetic materials, to modulate cell and tissue properties. These three strategies offer distinct stimulation routes given specific material characteristics. This review will evaluate material properties and biological response for these stimulation strategies with respect to their potential applications in neural and musculoskeletal research.
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Affiliation(s)
- Suleyman A Omer
- Department of Biomedical Engineering, The University of Arizona, Tucson, AZ, USA
| | - Kaitlyn H McKnight
- Department of Biomedical Engineering, The University of Arizona, Tucson, AZ, USA
| | - Lucas I Young
- Department of Biomedical Engineering, The University of Arizona, Tucson, AZ, USA
| | - Shang Song
- Department of Biomedical Engineering, The University of Arizona, Tucson, AZ, USA.
- Departments of Neuroscience GIDP, Materials Science and Engineering, BIO5 Institute, The University of Arizona, Tucson, AZ, USA.
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Lei C, Song JH, Li S, Zhu YN, Liu MY, Wan MC, Mu Z, Tay FR, Niu LN. Advances in materials-based therapeutic strategies against osteoporosis. Biomaterials 2023; 296:122066. [PMID: 36842238 DOI: 10.1016/j.biomaterials.2023.122066] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Revised: 02/16/2023] [Accepted: 02/18/2023] [Indexed: 02/22/2023]
Abstract
Osteoporosis is caused by the disruption in homeostasis between bone formation and bone resorption. Conventional management of osteoporosis involves systematic drug administration and hormonal therapy. These treatment strategies have limited curative efficacy and multiple adverse effects. Biomaterials-based therapeutic strategies have recently emerged as promising alternatives for the treatment of osteoporosis. The present review summarizes the current status of biomaterials designed for managing osteoporosis. The advantages of biomaterials-based strategies over conventional systematic drug treatment are presented. Different anti-osteoporotic delivery systems are concisely addressed. These materials include injectable hydrogels and nanoparticles, as well as anti-osteoporotic bone tissue engineering materials. Fabrication techniques such as 3D printing, electrostatic spinning and artificial intelligence are appraised in the context of how the use of these adjunctive techniques may improve treatment efficacy. The limitations of existing biomaterials are critically analyzed, together with deliberation of the future directions in biomaterials-based therapies. The latter include discussion on the use of combination strategies to enhance therapeutic efficacy in the osteoporosis niche.
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Affiliation(s)
- Chen Lei
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Jing-Han Song
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Song Li
- School of Stomatology, Xinjiang Medical University. Urumqi 830011, China
| | - Yi-Na Zhu
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Ming-Yi Liu
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Mei-Chen Wan
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Zhao Mu
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
| | - Franklin R Tay
- The Dental College of Georgia, Augusta University, Augusta, GA, 30912, USA.
| | - Li-Na Niu
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
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Zhao H, Liu C, Liu Y, Ding Q, Wang T, Li H, Wu H, Ma T. Harnessing electromagnetic fields to assist bone tissue engineering. Stem Cell Res Ther 2023; 14:7. [PMID: 36631880 PMCID: PMC9835389 DOI: 10.1186/s13287-022-03217-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 12/08/2022] [Indexed: 01/13/2023] Open
Abstract
Bone tissue engineering (BTE) emerged as one of the exceptional means for bone defects owing to it providing mechanical supports to guide bone tissue regeneration. Great advances have been made to facilitate the success of BTE in regenerating bone within defects. The use of externally applied fields has been regarded as an alternative strategy for BTE. Electromagnetic fields (EMFs), known as a simple and non-invasive therapy, can remotely provide electric and magnetic stimulation to cells and biomaterials, thus applying EMFs to assist BTE would be a promising strategy for bone regeneration. When combined with BTE, EMFs improve cell adhesion to the material surface by promoting protein adsorption. Additionally, EMFs have positive effects on mesenchymal stem cells and show capabilities of pro-angiogenesis and macrophage polarization manipulation. These advantages of EMFs indicate that it is perfectly suitable for representing the adjuvant treatment of BTE. We also summarize studies concerning combinations of EMFs and diverse biomaterial types. The strategy of combining EMFs and BTE receives encouraging outcomes and holds a promising future for effectively treating bone defects.
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Affiliation(s)
- Hongqi Zhao
- grid.33199.310000 0004 0368 7223Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei China
| | - Chaoxu Liu
- grid.33199.310000 0004 0368 7223Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei China
| | - Yang Liu
- grid.33199.310000 0004 0368 7223Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei China
| | - Qing Ding
- grid.33199.310000 0004 0368 7223Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei China
| | - Tianqi Wang
- grid.33199.310000 0004 0368 7223Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei China
| | - Hao Li
- grid.33199.310000 0004 0368 7223Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei China
| | - Hua Wu
- Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
| | - Tian Ma
- Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
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Organoids and Their Research Progress in Plastic and Reconstructive Surgery. Aesthetic Plast Surg 2022; 47:880-891. [PMID: 36401134 DOI: 10.1007/s00266-022-03129-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 09/25/2022] [Indexed: 11/19/2022]
Abstract
Organoids are 3D structures generated from stem cells. Their functions and physiological characteristics are similar to those of normal organs. They are used in disease mechanism research, new drug development, organ transplantation and other fields. In recent years, the application of 3D materials in plastic surgery for repairing injuries, filling, tissue reconstruction and regeneration has also been investigated. The PubMed/MEDLINE database was queried to search for animal and human studies published through July of 2022 with search terms related to Organoids, Plastic Surgery, Pluripotent Stem Cells, Bioscaffold, Skin Reconstruction, Bone and Cartilage Regeneration. This review presents stem cells, scaffold materials and methods for the construction of organoids for plastic surgery, and it summarizes their research progress in plastic surgery in recent years.Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Kyykallio H, Faria AVS, Hartman R, Capra J, Rilla K, Siljander PR. A quick pipeline for the isolation of 3D cell culture-derived extracellular vesicles. J Extracell Vesicles 2022; 11:e12273. [PMID: 36257915 PMCID: PMC9579059 DOI: 10.1002/jev2.12273] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 08/10/2021] [Accepted: 09/27/2022] [Indexed: 11/12/2022] Open
Abstract
Recent advances in cell biology research regarding extracellular vesicles have highlighted an increasing demand to obtain 3D cell culture-derived EVs, because they are considered to more accurately represent EVs obtained in vivo. However, there is still a grave need for efficient and tunable methodologies to isolate EVs from 3D cell cultures. Using nanofibrillar cellulose (NFC) scaffold as a 3D cell culture matrix, we developed a pipeline of two different approaches for EV isolation from cancer spheroids. A batch method was created for delivering high EV yield at the end of the culture period, and a harvesting method was created to enable time-dependent collection of EVs to combine EV profiling with spheroid development. Both these methods were easy to set up, quick to perform, and they provided a high EV yield. When compared to scaffold-free 3D spheroid cultures on ultra-low affinity plates, the NFC method resulted in similar EV production/cell, but the NFC method was scalable and easier to perform resulting in high EV yields. In summary, we introduce here an NFC-based, innovative pipeline for acquiring EVs from 3D cancer spheroids, which can be tailored to support the needs of variable EV research objectives.
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Affiliation(s)
- Heikki Kyykallio
- Institute of BiomedicineUniversity of Eastern FinlandKuopioFinland
| | - Alessandra V. S. Faria
- EV GroupMolecular and Integrative Biosciences Research ProgrammeFaculty of Biological and Environmental SciencesUniversity of HelsinkiHelsinkiFinland
| | - Rosabella Hartman
- EV GroupMolecular and Integrative Biosciences Research ProgrammeFaculty of Biological and Environmental SciencesUniversity of HelsinkiHelsinkiFinland
| | - Janne Capra
- Institute of BiomedicineUniversity of Eastern FinlandKuopioFinland
| | - Kirsi Rilla
- Institute of BiomedicineUniversity of Eastern FinlandKuopioFinland
| | - Pia R‐M Siljander
- EV GroupMolecular and Integrative Biosciences Research ProgrammeFaculty of Biological and Environmental SciencesUniversity of HelsinkiHelsinkiFinland
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Yao H, Zhang L, Yan S, He Y, Zhu H, Li Y, Wang D, Yang K. Low-intensity pulsed ultrasound/nanomechanical force generators enhance osteogenesis of BMSCs through microfilaments and TRPM7. J Nanobiotechnology 2022; 20:378. [PMID: 35964037 PMCID: PMC9375242 DOI: 10.1186/s12951-022-01587-3] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 08/03/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Low-intensity pulsed ultrasound (LIPUS) has been reported to accelerate fracture healing, but the mechanism is unclear and its efficacy needs to be further optimized. Ultrasound in combination with functionalized microbubbles has been shown to induce local shear forces and controllable mechanical stress in cells, amplifying the mechanical effects of LIPUS. Nanoscale lipid bubbles (nanobubbles) have high stability and good biosafety. However, the effect of LIPUS combined with functionalized nanobubbles on osteogenesis has rarely been studied. RESULTS In this study, we report cyclic arginine-glycine-aspartic acid-modified nanobubbles (cRGD-NBs), with a particle size of ~ 500 nm, able to actively target bone marrow mesenchymal stem cells (BMSCs) via integrin receptors. cRGD-NBs can act as nanomechanical force generators on the cell membrane, and further enhance the BMSCs osteogenesis and bone formation promoted by LIPUS. The polymerization of actin microfilaments and the mechanosensitive transient receptor potential melastatin 7 (TRPM7) ion channel play important roles in BMSCs osteogenesis promoted by LIPUS/cRGD-NBs. Moreover, the mutual regulation of TRPM7 and actin microfilaments promote the effect of LIPUS/cRGD-NBs. The extracellular Ca2 + influx, controlled partly by TRPM7, could participated in the effect of LIPUS/cRGD-NBs on BMSCs. CONCLUSIONS The nanomechanical force generators cRGD-NBs could promote osteogenesis of BMSCs and bone formation induced by LIPUS, through regulation TRPM7, actin cytoskeleton, and intracellular calcium oscillations. This study provides new directions for optimizing the efficacy of LIPUS for fracture healing, and a theoretical basis for the further application and development of LIPUS in clinical practice.
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Affiliation(s)
- Huan Yao
- Pediatric Research Institute, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing, 400014, China.,Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Liang Zhang
- Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Shujin Yan
- Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Yiman He
- Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Hui Zhu
- Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Yasha Li
- Pediatric Research Institute, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing, 400014, China
| | - Dong Wang
- Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Ke Yang
- Pediatric Research Institute, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing, 400014, China.
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Frazier TP, Hamel K, Wu X, Rogers E, Lassiter H, Robinson J, Mohiuddin O, Henderson M, Gimble JM. Adipose-derived cells: building blocks of three-dimensional microphysiological systems. BIOMATERIALS TRANSLATIONAL 2021; 2:301-306. [PMID: 35837416 PMCID: PMC9255798 DOI: 10.12336/biomatertransl.2021.04.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 12/15/2021] [Accepted: 12/20/2021] [Indexed: 11/15/2022]
Abstract
Microphysiological systems (MPS) created with human-derived cells and biomaterial scaffolds offer a potential in vitro alternative to in vivo animal models. The adoption of three-dimensional MPS models has economic, ethical, regulatory, and scientific implications for the fields of regenerative medicine, metabolism/obesity, oncology, and pharmaceutical drug discovery. Key opinion leaders acknowledge that MPS tools are uniquely positioned to aid in the objective to reduce, refine, and eventually replace animal experimentation while improving the accuracy of the finding's clinical translation. Adipose tissue has proven to be an accessible and available source of human-derived stromal vascular fraction (SVF) cells, a heterogeneous population available at point of care, and adipose-derived stromal/stem cells, a relatively homogeneous population requiring plastic adherence and culture expansion of the SVF cells. The adipose-derived stromal/stem cells or SVF cells, in combination with human tissue or synthetic biomaterial scaffolds, can be maintained for extended culture periods as three-dimensional MPS models under angiogenic, stromal, adipogenic, or osteogenic conditions. This review highlights recent literature relating to the versatile use of adipose-derived cells as fundamental components of three-dimensional MPS models for discovery research and development. In this context, it compares the merits and limitations of the adipose-derived stromal/stem cells relative to SVF cell models and considers the likely directions that this emerging field of scientific discovery will take in the near future.
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Affiliation(s)
- Trivia P. Frazier
- Obatala Sciences Inc., New Orleans, LA, USA,Corresponding author: Trivia Frazier,
| | | | - Xiying Wu
- Obatala Sciences Inc., New Orleans, LA, USA
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Pitsalidis C, Pappa AM, Boys AJ, Fu Y, Moysidou CM, van Niekerk D, Saez J, Savva A, Iandolo D, Owens RM. Organic Bioelectronics for In Vitro Systems. Chem Rev 2021; 122:4700-4790. [PMID: 34910876 DOI: 10.1021/acs.chemrev.1c00539] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Bioelectronics have made strides in improving clinical diagnostics and precision medicine. The potential of bioelectronics for bidirectional interfacing with biology through continuous, label-free monitoring on one side and precise control of biological activity on the other has extended their application scope to in vitro systems. The advent of microfluidics and the considerable advances in reliability and complexity of in vitro models promise to eventually significantly reduce or replace animal studies, currently the gold standard in drug discovery and toxicology testing. Bioelectronics are anticipated to play a major role in this transition offering a much needed technology to push forward the drug discovery paradigm. Organic electronic materials, notably conjugated polymers, having demonstrated technological maturity in fields such as solar cells and light emitting diodes given their outstanding characteristics and versatility in processing, are the obvious route forward for bioelectronics due to their biomimetic nature, among other merits. This review highlights the advances in conjugated polymers for interfacing with biological tissue in vitro, aiming ultimately to develop next generation in vitro systems. We showcase in vitro interfacing across multiple length scales, involving biological models of varying complexity, from cell components to complex 3D cell cultures. The state of the art, the possibilities, and the challenges of conjugated polymers toward clinical translation of in vitro systems are also discussed throughout.
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Affiliation(s)
- Charalampos Pitsalidis
- Department of Physics, Khalifa University of Science and Technology, P.O. Box 127788, Abu Dhabi 127788, UAE.,Department of Chemical Engineering and Biotechnology, University of Cambridge Philippa Fawcett Drive, Cambridge CB3 0AS, U.K
| | - Anna-Maria Pappa
- Department of Biomedical Engineering, Khalifa University of Science and Technology, P.O. Box 127788, Abu Dhabi 127788, UAE
| | - Alexander J Boys
- Department of Chemical Engineering and Biotechnology, University of Cambridge Philippa Fawcett Drive, Cambridge CB3 0AS, U.K
| | - Ying Fu
- Department of Chemical Engineering and Biotechnology, University of Cambridge Philippa Fawcett Drive, Cambridge CB3 0AS, U.K.,Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, Glasgow G1 1RD, U.K
| | - Chrysanthi-Maria Moysidou
- Department of Chemical Engineering and Biotechnology, University of Cambridge Philippa Fawcett Drive, Cambridge CB3 0AS, U.K
| | - Douglas van Niekerk
- Department of Chemical Engineering and Biotechnology, University of Cambridge Philippa Fawcett Drive, Cambridge CB3 0AS, U.K
| | - Janire Saez
- Department of Chemical Engineering and Biotechnology, University of Cambridge Philippa Fawcett Drive, Cambridge CB3 0AS, U.K.,Microfluidics Cluster UPV/EHU, BIOMICs Microfluidics Group, Lascaray Research Center, University of the Basque Country UPV/EHU, Avenida Miguel de Unamuno, 3, 01006 Vitoria-Gasteiz, Spain.,Ikerbasque, Basque Foundation for Science, E-48011 Bilbao, Spain
| | - Achilleas Savva
- Department of Chemical Engineering and Biotechnology, University of Cambridge Philippa Fawcett Drive, Cambridge CB3 0AS, U.K
| | - Donata Iandolo
- INSERM, U1059 Sainbiose, Université Jean Monnet, Mines Saint-Étienne, Université de Lyon, 42023 Saint-Étienne, France
| | - Róisín M Owens
- Department of Chemical Engineering and Biotechnology, University of Cambridge Philippa Fawcett Drive, Cambridge CB3 0AS, U.K
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Widera D. Recent Advances in Translational Adipose-Derived Stem Cell Biology. Biomolecules 2021; 11:biom11111660. [PMID: 34827658 PMCID: PMC8615724 DOI: 10.3390/biom11111660] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 11/05/2021] [Indexed: 12/30/2022] Open
Affiliation(s)
- Darius Widera
- Stem Cell Biology and Regenerative Medicine Group, School of Pharmacy, University of Reading, Reading RG6 6UB, UK
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Cheah YJ, Buyong MR, Mohd Yunus MH. Wound Healing with Electrical Stimulation Technologies: A Review. Polymers (Basel) 2021; 13:3790. [PMID: 34771347 PMCID: PMC8588136 DOI: 10.3390/polym13213790] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 10/16/2021] [Accepted: 10/29/2021] [Indexed: 01/22/2023] Open
Abstract
Electrical stimulation (ES) is an attractive field among clinicians in the topic of wound healing, which is common yet complicated and requires multidisciplinary approaches. The conventional dressing and skin graft showed no promise on complete wound closure. These urge the need for the exploration of electrical stimulation to supplement current wound care management. This review aims to provide an overview of electrical stimulation in wound healing. The mechanism of galvanotaxis related to wound repair will be reviewed at the cellular and molecular levels. Meanwhile, different modalities of externally applied electricity mimicking a physiologic electric field will be discussed and compared in vitro, in vivo, and clinically. With the emerging of tissue engineering and regenerative medicine, the integration of electroconductive biomaterials into modern miniaturised dressing is of interest and has become possible with the advancing understanding of smart biomaterials.
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Affiliation(s)
- Yt Jun Cheah
- Department of Physiology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur 56600, Malaysia;
| | - Muhamad Ramdzan Buyong
- Institute of Microengineering and Nanoelectronics, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia;
| | - Mohd Heikal Mohd Yunus
- Department of Physiology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur 56600, Malaysia;
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Lee MH, Park YJ, Hong SH, Koo MA, Cho M, Park JC. Pulsed Electrical Stimulation Enhances Consistency of Directional Migration of Adipose-Derived Stem Cells. Cells 2021; 10:cells10112846. [PMID: 34831069 PMCID: PMC8616144 DOI: 10.3390/cells10112846] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 09/16/2021] [Accepted: 10/20/2021] [Indexed: 12/31/2022] Open
Abstract
Electrical stimulation is a well-known strategy for regulating cell behavior, both in pathological and physiological processes such as wound healing, tissue regeneration, and embryonic development. Electrotaxis is the directional migration of cells toward the cathode or anode when subjected to electrical stimulation. In this study, we investigated the conditions for enhanced directional migration of electrically stimulated adipose-derived stem cells (ADSCs) during prolonged culture, using a customized agar-salt electrotaxis chamber. Exposure of ADSCs to a 1200 μA electric current for 3 h, followed by cessation of stimulation for 6 h and resumed stimulation for a further 3 h, increased directional cell migration toward the anode without inducing cell death. Moreover, Golgi polarization maintained the direction of polarity parallel to the direction of cell movement. Herein, we demonstrated that a pulsed electric current is sufficient to trigger directional migration of ADSCs in long-term culture while maintaining cell viability.
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Affiliation(s)
- Mi Hee Lee
- Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, Seoul 03722, Korea; (M.H.L.); (Y.J.P.); (S.H.H.); (M.-A.K.); (M.C.)
| | - Ye Jin Park
- Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, Seoul 03722, Korea; (M.H.L.); (Y.J.P.); (S.H.H.); (M.-A.K.); (M.C.)
- Department of Medical Device Engineering and Management, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Seung Hee Hong
- Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, Seoul 03722, Korea; (M.H.L.); (Y.J.P.); (S.H.H.); (M.-A.K.); (M.C.)
- Department of Medical Engineering, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Min-Ah Koo
- Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, Seoul 03722, Korea; (M.H.L.); (Y.J.P.); (S.H.H.); (M.-A.K.); (M.C.)
- Department of Medical Engineering, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Minyoung Cho
- Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, Seoul 03722, Korea; (M.H.L.); (Y.J.P.); (S.H.H.); (M.-A.K.); (M.C.)
| | - Jong-Chul Park
- Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, Seoul 03722, Korea; (M.H.L.); (Y.J.P.); (S.H.H.); (M.-A.K.); (M.C.)
- Department of Medical Device Engineering and Management, Yonsei University College of Medicine, Seoul 03722, Korea
- Department of Medical Engineering, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea
- Correspondence: ; Tel.: +82-2-2228-1917
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Torre EC, Bicer M, Cottrell GS, Widera D, Tamagnini F. Time-Dependent Reduction of Calcium Oscillations in Adipose-Derived Stem Cells Differentiating towards Adipogenic and Osteogenic Lineage. Biomolecules 2021; 11:biom11101400. [PMID: 34680033 PMCID: PMC8533133 DOI: 10.3390/biom11101400] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 09/16/2021] [Accepted: 09/20/2021] [Indexed: 12/11/2022] Open
Abstract
Adipose-derived mesenchymal stromal cells (ASCs) are multipotent stem cells which can differentiate into various cell types, including osteocytes and adipocytes. Due to their ease of harvesting, multipotency, and low tumorigenicity, they are a prime candidate for the development of novel interventional approaches in regenerative medicine. ASCs exhibit slow, spontaneous Ca2+ oscillations and the manipulation of Ca2+ signalling via electrical stimulation was proposed as a potential route for promoting their differentiation in vivo. However, the effects of differentiation-inducing treatments on spontaneous Ca2+ oscillations in ASCs are not yet fully characterised. In this study, we used 2-photon live Ca2+ imaging to assess the fraction of cells showing spontaneous oscillations and the frequency of the oscillation (measured as interpeak interval—IPI) in ASCs undergoing osteogenic or adipogenic differentiation, using undifferentiated ASCs as controls. The measurements were carried out at 7, 14, and 21 days in vitro (DIV) to assess the effect of time in culture on Ca2+ dynamics. We observed that both time and differentiation treatment are important factors associated with a reduced fraction of cells showing Ca2+ oscillations, paralleled by increased IPI times, in comparison with untreated ASCs. Both adipogenic and osteogenic differentiation resulted in a reduction in Ca2+ dynamics, such as the fraction of cells showing intracellular Ca2+ oscillations and their frequency. Adipogenic differentiation was associated with a more pronounced reduction of Ca2+ dynamics compared to cells differentiating towards the osteogenic fate. Changes in Ca2+ associated oscillations with a specific treatment had already occurred at 7 DIV. Finally, we observed a reduction in Ca2+ dynamics over time in untreated ASCs. These data suggest that adipogenic and osteogenic differentiation cell fates are associated with specific changes in spontaneous Ca2+ dynamics over time. While this observation is interesting and provides useful information to understand the functional correlates of stem cell differentiation, further studies are required to clarify the molecular and mechanistic correlates of these changes. This will allow us to better understand the causal relationship between Ca2+ dynamics and differentiation, potentially leading to the development of novel, more effective interventions for both bone regeneration and control of adipose growth.
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Affiliation(s)
- Enrico C. Torre
- Stem Cell Biology and Regenerative Medicine Group, School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6LA, UK; (E.C.T.); (M.B.)
- Neuronal and Cellular Physiology Group, School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6LA, UK
- Biomedicine West Wing, International Centre for Life, Times Square, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK
| | - Mesude Bicer
- Stem Cell Biology and Regenerative Medicine Group, School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6LA, UK; (E.C.T.); (M.B.)
- Department of Bioengineering, Sumer Campus, Abdullah Gül University, Kayseri 38080, Turkey
| | - Graeme S. Cottrell
- Cellular and Molecular Neuroscience, School of Pharmacy, University of Reading, Reading RG6 6LA, UK;
| | - Darius Widera
- Stem Cell Biology and Regenerative Medicine Group, School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6LA, UK; (E.C.T.); (M.B.)
- Correspondence: (D.W.); (F.T.)
| | - Francesco Tamagnini
- Neuronal and Cellular Physiology Group, School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6LA, UK
- Correspondence: (D.W.); (F.T.)
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