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Jeyaraman N, Jeyaraman M, Muthu S, Balaji S, Ramasubramanian S, Patro BP. Chondrogenic Potential of Umbilical Cord-Derived Mesenchymal Stromal Cells: Insights and Innovations. Indian J Orthop 2024; 58:1349-1361. [PMID: 39324097 PMCID: PMC11420429 DOI: 10.1007/s43465-024-01239-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Accepted: 08/14/2024] [Indexed: 09/11/2024]
Abstract
BACKGROUND The advent of tissue engineering and regenerative medicine has introduced innovative approaches to treating degenerative and traumatic injuries, particularly in cartilage, a tissue with limited self-repair capabilities. Among the various stem cell sources, umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have garnered significant interest due to their non-invasive collection, minimal ethical concerns, and robust regenerative potential, particularly in cartilage regeneration. METHODS A comprehensive literature review was conducted using multiple databases, including PubMed, Scopus, Web of Science, and Google Scholar. Search terms focused on "umbilical cordderived mesenchymal stromal cells," "chondrogenesis," "cartilage regeneration," and related topics. Studies published in the past two decades were included, with selection criteria emphasizing methodological rigor and relevance to UC-MSC chondrogenesis. The review synthesizes findings from various sources to provide a thorough analysis of the potential of UC-MSCs in cartilage tissue engineering. RESULTS UC-MSCs exhibit significant chondrogenic potential, supported by their ability to differentiate into chondrocytes under specific conditions. Recent advancements include the development of biomaterial scaffolds and the application of genetic engineering techniques, such as CRISPR/Cas9, to enhance chondrogenic differentiation. Despite these advancements, challenges remain in standardizing cell isolation techniques, scaling up production for clinical use, and ensuring the long-term functionality of regenerated cartilage. CONCLUSION UC-MSCs offer a promising solution for cartilage regeneration in the field of regenerative medicine. Ongoing research is focused on overcoming current challenges through the use of advanced technologies, including bioreactors and gene editing. Collaborative efforts among researchers, clinicians, and bioengineers are essential to translating the potential of UC-MSCs into effective clinical therapies, which could significantly advance tissue regeneration and therapeutic innovation.
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Affiliation(s)
- Naveen Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Tamil Nadu, Chennai, 600077 India
| | - Madhan Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Tamil Nadu, Chennai, 600077 India
- VirginiaTech India, Dr MGR Educational and Research Institute, Tamil Nadu, Chennai, 600095 India
- Department of Orthopaedics, Orthopaedic Research Group, Tamil Nadu, Coimbatore, 641045 India
| | - Sathish Muthu
- Department of Orthopaedics, Orthopaedic Research Group, Tamil Nadu, Coimbatore, 641045 India
- Department of Biotechnology, Faculty of Engineering, Karpagam Academy of Higher Education, Tamil Nadu, Coimbatore, 641021 India
- Department of Orthopaedics, Government Karur Medical College, Tamil Nadu, Karur, 639004 India
| | - Sangeetha Balaji
- Department of Orthopaedics, Government Medical College, Omandurar Government Estate, Tamil Nadu, Chennai, 600002 India
| | - Swaminathan Ramasubramanian
- Department of Orthopaedics, Government Medical College, Omandurar Government Estate, Tamil Nadu, Chennai, 600002 India
| | - Bishnu Prasad Patro
- Department of Orthopaedics, All India Institute of Medical Sciences, Bhubaneswar, Odisha 751019 India
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Sun L, Xu Y, Han Y, Cui J, Jing Z, Li D, Liu J, Xiao C, Li D, Cai B. Collagen-Based Hydrogels for Cartilage Regeneration. Orthop Surg 2023; 15:3026-3045. [PMID: 37942509 PMCID: PMC10694028 DOI: 10.1111/os.13884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 08/13/2023] [Accepted: 08/15/2023] [Indexed: 11/10/2023] Open
Abstract
Cartilage regeneration remains difficult due to a lack of blood vessels. Degradation of the extracellular matrix (ECM) causes cartilage defects, and the ECM provides the natural environment and nutrition for cartilage regeneration. Until now, collagen hydrogels are considered to be excellent material for cartilage regeneration due to the similar structure to ECM and good biocompatibility. However, collagen hydrogels also have several drawbacks, such as low mechanical strength, limited ability to induce stem cell differentiation, and rapid degradation. Thus, there is a demanding need to optimize collagen hydrogels for cartilage regeneration. In this review, we will first briefly introduce the structure of articular cartilage and cartilage defect classification and collagen, then provide an overview of the progress made in research on collagen hydrogels with chondrocytes or stem cells, comprehensively expound the research progress and clinical applications of collagen-based hydrogels that integrate inorganic or organic materials, and finally present challenges for further clinical translation.
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Affiliation(s)
- Lihui Sun
- Division of Bone and Joint Surgery, Center of OrthopaedicsFirst Hospital of Jilin UniversityChangchunPeople's Republic of China
| | - Yan Xu
- Division of Bone and Joint Surgery, Center of OrthopaedicsFirst Hospital of Jilin UniversityChangchunPeople's Republic of China
| | - Yu Han
- Division of Bone and Joint Surgery, Center of OrthopaedicsFirst Hospital of Jilin UniversityChangchunPeople's Republic of China
| | - Jing Cui
- Jilin Provincial Key Laboratory of Oral Biomedical Engineering, School and Hospital of StomatologyJilin UniversityChangchunChina
| | - Zheng Jing
- Division of Bone and Joint Surgery, Center of OrthopaedicsFirst Hospital of Jilin UniversityChangchunPeople's Republic of China
| | - Dongbo Li
- Division of Bone and Joint Surgery, Center of OrthopaedicsFirst Hospital of Jilin UniversityChangchunPeople's Republic of China
| | - Jianguo Liu
- Division of Bone and Joint Surgery, Center of OrthopaedicsFirst Hospital of Jilin UniversityChangchunPeople's Republic of China
| | - Chunsheng Xiao
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchunPeople's Republic of China
| | - Dongsong Li
- Division of Bone and Joint Surgery, Center of OrthopaedicsFirst Hospital of Jilin UniversityChangchunPeople's Republic of China
| | - Bo Cai
- Department of Ultrasound DiagnosisThe 964 Hospital of Chinese People's Liberation ArmyChangchunPeople's Republic of China
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Liu S, Chi Y, Wu X, Zhu B, Wang H, Liang Y, Wang Y. Fat Stem Cells Combined with Complement C3 Inhibits the Progress of Type 2 Diabetes in Rats. J BIOMATER TISS ENG 2022. [DOI: 10.1166/jbt.2022.3052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
This study assessed the effect of fat stem cells combined with complement C3 on Wnt/β-catenin pathway in type 2 diabetic rats. 30 male rats were randomly and equally divided into group of type 2 diabetes (intraperitoneal injection of urea with cephalosporins at a dose of
30 mg/kg and fed with high sugar and fat), type 2 diabetes+adipose stem cells+C3 group (after adipose stem cells+C3 group) and control group. Rats in adipose stem cells+C3 group received administration of stem cells and C3. The model of type 2 diabetic rats was successfully constructed. The
blood glucose of type 2 diabetic rats and fat stem cell+C3 group was significantly higher than 11.1 mmol/L. Adipocyte was induced to be differentiated into islet cells depending on insulin secretion and glucose concentration. The combination of complement C3 improved the glucose sensitivity
in type 2 diabetic rats. Compared with diabetic group, β-catenin and TCF in fat stem cell+C3 group were significantly decreased (P < 0.05). In conclusion, fat stem cells combined with complement C3 inhibit the disease progression in type 2 diabetic rats possibly by inhibiting
the activation of Wnt/β-catenin signaling pathway.
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Affiliation(s)
- Shuang Liu
- Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China
| | - Yangfeng Chi
- Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China
| | - Xinye Wu
- Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China
| | - Bingbing Zhu
- Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China
| | - Hao Wang
- Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China
| | - Yongping Liang
- Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China
| | - Yunman Wang
- Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China
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Sonthithai P, Hankamonsiri W, Lertwimol T, Uppanan P, Janvikul W. Novel modified culture medium for enhancing redifferentiation of chondrocytes for cartilage tissue engineering applications. Biotechnol Prog 2022; 38:e3240. [DOI: 10.1002/btpr.3240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Revised: 01/17/2022] [Accepted: 01/21/2022] [Indexed: 11/09/2022]
Affiliation(s)
- Pacharapan Sonthithai
- Biofunctional Materials and Devices Research Group, National Metal and Materials Technology Center, 114 Thailand Science Park Phahonyothin Road, Klong Luang, Pathum Thani 12120 Thailand
| | - Weerawan Hankamonsiri
- Biofunctional Materials and Devices Research Group, National Metal and Materials Technology Center, 114 Thailand Science Park Phahonyothin Road, Klong Luang, Pathum Thani 12120 Thailand
| | - Tareerat Lertwimol
- Biofunctional Materials and Devices Research Group, National Metal and Materials Technology Center, 114 Thailand Science Park Phahonyothin Road, Klong Luang, Pathum Thani 12120 Thailand
| | - Paweena Uppanan
- Biofunctional Materials and Devices Research Group, National Metal and Materials Technology Center, 114 Thailand Science Park Phahonyothin Road, Klong Luang, Pathum Thani 12120 Thailand
| | - Wanida Janvikul
- Biofunctional Materials and Devices Research Group, National Metal and Materials Technology Center, 114 Thailand Science Park Phahonyothin Road, Klong Luang, Pathum Thani 12120 Thailand
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Um S, Ha J, Choi SJ, Oh W, Jin HJ. Prospects for the therapeutic development of umbilical cord blood-derived mesenchymal stem cells. World J Stem Cells 2020; 12:1511-1528. [PMID: 33505598 PMCID: PMC7789129 DOI: 10.4252/wjsc.v12.i12.1511] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 10/23/2020] [Accepted: 11/12/2020] [Indexed: 02/06/2023] Open
Abstract
Umbilical cord blood (UCB) is a primitive and abundant source of mesenchymal stem cells (MSCs). UCB-derived MSCs have a broad and efficient therapeutic capacity to treat various diseases and disorders. Despite the high latent self-renewal and differentiation capacity of these cells, the safety, efficacy, and yield of MSCs expanded for ex vivo clinical applications remains a concern. However, immunomodulatory effects have emerged in various disease models, exhibiting specific mechanisms of action, such as cell migration and homing, angiogenesis, anti-apoptosis, proliferation, anti-cancer, anti-fibrosis, anti-inflammation and tissue regeneration. Herein, we review the current literature pertaining to the UCB-derived MSC application as potential treatment strategies, and discuss the concerns regarding the safety and mass production issues in future applications.
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Affiliation(s)
- Soyoun Um
- Research Team for Immune Cell Therapy, Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
| | - Jueun Ha
- Research Team for Osteoarthritis, Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
| | - Soo Jin Choi
- Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
| | - Wonil Oh
- Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
| | - Hye Jin Jin
- Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
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Arrigoni C, D’Arrigo D, Rossella V, Candrian C, Albertini V, Moretti M. Umbilical Cord MSCs and Their Secretome in the Therapy of Arthritic Diseases: A Research and Industrial Perspective. Cells 2020; 9:cells9061343. [PMID: 32481562 PMCID: PMC7348802 DOI: 10.3390/cells9061343] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 05/20/2020] [Accepted: 05/26/2020] [Indexed: 02/06/2023] Open
Abstract
The prevalence of arthritic diseases is increasing in developed countries, but effective treatments are currently lacking. The injection of mesenchymal stem cells (MSCs) represents a promising approach to counteract the degenerative and inflammatory environment characterizing those pathologies, such as osteoarthritis (OA). However, the majority of clinical approaches based on MSCs are used within an autologous paradigm, with important limitations. For this reason, allogeneic MSCs isolated from cord blood (cbMSCs) and Wharton’s jelly (wjMSCs) gained increasing interest, demonstrating promising results in this field. Moreover, recent evidences shows that MSCs beneficial effects can be related to their secretome rather than to the presence of cells themselves. Among the trophic factors secreted by MSCs, extracellular vesicles (EVs) are emerging as a promising candidate for the treatment of arthritic joints. In the present review, the application of umbilical cord MSCs and their secretome as innovative therapeutic approaches in the treatment of arthritic joints will be examined. With the prospective of routine clinical applications, umbilical cord MSCs and EVs will be discussed also within an industrial and regulatory perspective.
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Affiliation(s)
- Chiara Arrigoni
- Regenerative Medicine Technologies Laboratory, Ente Ospedaliero Cantonale (EOC), via Tesserete 46, 6900 Lugano, Switzerland; (C.A.); (D.D.)
| | - Daniele D’Arrigo
- Regenerative Medicine Technologies Laboratory, Ente Ospedaliero Cantonale (EOC), via Tesserete 46, 6900 Lugano, Switzerland; (C.A.); (D.D.)
| | - Valeria Rossella
- Swiss Stem Cells Biotech, Via Pizzamiglio 12, 6833 Vacallo, Switzerland; (V.R.); (V.A.)
| | - Christian Candrian
- Unità di Ortopedia e Traumatologia, Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale (EOC), via Tesserete 46, 6900 Lugano, Switzerland;
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Via Buffi 13, 6900 Lugano, Switzerland
| | - Veronica Albertini
- Swiss Stem Cells Biotech, Via Pizzamiglio 12, 6833 Vacallo, Switzerland; (V.R.); (V.A.)
| | - Matteo Moretti
- Regenerative Medicine Technologies Laboratory, Ente Ospedaliero Cantonale (EOC), via Tesserete 46, 6900 Lugano, Switzerland; (C.A.); (D.D.)
- Cell and Tissue Engineering Laboratory, IRCCS Istituto Ortopedico Galeazzi, via R. Galeazzi 4., 20161 Milano, Italy
- Correspondence: ; Tel.: +41-91-811-7076
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7
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Zhang J, Zhao J, Mao Q, Xia H. A simple, efficient and economical method for isolating and culturing human umbilical cord blood‑derived mesenchymal stromal cells. Mol Med Rep 2019; 20:5257-5264. [PMID: 31661118 DOI: 10.3892/mmr.2019.10767] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2019] [Accepted: 09/23/2019] [Indexed: 11/05/2022] Open
Abstract
Mesenchymal stromal cells (MSCs) hold broad therapeutic potential in various diseases, however, it is difficult to produce sufficient numbers of MSCs for clinical application, therefore, improved culture systems are required. The present study aimed to develop a novel method for isolating and culturing human umbilical cord blood‑derived mesenchymal stromal cells (hUCB‑MSCs). A sequential culture method was developed that uses two types of culture media to optimize the isolation and culture of hUCB‑MSCs. First, DMEM supplemented with mesenchymal stem cell growth supplement was used to improve the colony formation and primary culture success rates of hUCB‑MSCs. Then, after removing the heterogeneous cell population, ordinary DMEM was used from the fourth passage. This method obtained hUCB‑MSCs with high culture efficiency and at a greatly reduced cost. The optimal culture conditions were determined and the hUCB‑MSCs were phenotypically characterized after passaging. Taken together, this simple, efficient and economical method can produce a large number of high‑quality hUCB‑MSCs in <1 month, therefore facilitating the future clinical applications of hUCB‑MSCs.
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Affiliation(s)
- Junhe Zhang
- Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi 710062, P.R. China
| | - Junli Zhao
- Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi 710062, P.R. China
| | - Qinwen Mao
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
| | - Haibin Xia
- Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi 710062, P.R. China
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Roberts EL, Dang T, Lepage SIM, Alizadeh AH, Walsh T, Koch TG, Kallos MS. Improved expansion of equine cord blood derived mesenchymal stromal cells by using microcarriers in stirred suspension bioreactors. J Biol Eng 2019; 13:25. [PMID: 30949237 PMCID: PMC6429778 DOI: 10.1186/s13036-019-0153-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Accepted: 02/22/2019] [Indexed: 12/22/2022] Open
Abstract
Equine mesenchymal stromal cells (MSCs) are increasingly investigated for their clinical therapeutic utility. Such cell-based treatments can require cell numbers in the millions or billions, with conventional expansion methods using static T-flasks typically inefficient in achieving these cell numbers. Equine cord blood-derived MSCs (eCB-MSCs), are promising cell candidates owing to their capacity for chondrogenic differentiation and immunomodulation. Expansion of eCB-MSCs in stirred suspension bioreactors with microcarriers as an attachment surface has the potential to generate clinically relevant numbers of cells while decreasing cost, time and labour requirements and increasing reproducibility and yield when compared to static expansion. As eCB-MSCs have not yet been expanded in stirred suspension bioreactors, a robust protocol was required to expand these cells using this method. This study outlines the development of an expansion bioprocess, detailing the inoculation phase, expansion phase, and harvesting phase, followed by phenotypic and trilineage differentiation characterization of two eCB-MSC donors. The process achieved maximum cell densities up to 75,000 cells/cm2 corresponding to 40 million cells in a 100 mL bioreactor, with a harvesting efficiency of up to 80%, corresponding to a yield of 32 million cells from a 100 mL bioreactor. When compared to cells grown in static T-flasks, bioreactor-expanded eCB-MSC cultures did not change in surface marker expression or trilineage differentiation capacity. This indicates that the bioreactor expansion process yields large quantities of eCB-MSCs with similar characteristics to conventionally grown eCB-MSCs.
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Affiliation(s)
- Erin L. Roberts
- Pharmaceutical Production Research Facility, Schulich School of Engineering, University of Calgary, 2500 University Dr. NW, Calgary, AB T2N 1N4 Canada
- Biomedical Engineering Graduate Program, University of Calgary, 2500 University Dr. NW, Calgary, AB T2N 1N4 Canada
| | - Tiffany Dang
- Pharmaceutical Production Research Facility, Schulich School of Engineering, University of Calgary, 2500 University Dr. NW, Calgary, AB T2N 1N4 Canada
- Biomedical Engineering Graduate Program, University of Calgary, 2500 University Dr. NW, Calgary, AB T2N 1N4 Canada
| | - Sarah I. M. Lepage
- Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Gordon St, Guelph, ON N1G 2W1 Canada
| | - Amir Hamed Alizadeh
- Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Gordon St, Guelph, ON N1G 2W1 Canada
| | - Tylor Walsh
- Pharmaceutical Production Research Facility, Schulich School of Engineering, University of Calgary, 2500 University Dr. NW, Calgary, AB T2N 1N4 Canada
- Biomedical Engineering Graduate Program, University of Calgary, 2500 University Dr. NW, Calgary, AB T2N 1N4 Canada
| | - Thomas G. Koch
- Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Gordon St, Guelph, ON N1G 2W1 Canada
| | - Michael S. Kallos
- Pharmaceutical Production Research Facility, Schulich School of Engineering, University of Calgary, 2500 University Dr. NW, Calgary, AB T2N 1N4 Canada
- Biomedical Engineering Graduate Program, University of Calgary, 2500 University Dr. NW, Calgary, AB T2N 1N4 Canada
- Department of Chemical and Petroleum Engineering, Schulich School of Engineering, University of Calgary, 2500 University Dr. NW, Calgary, AB T2N 1N4 Canada
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Graceffa V, Vinatier C, Guicheux J, Stoddart M, Alini M, Zeugolis DI. Chasing Chimeras - The elusive stable chondrogenic phenotype. Biomaterials 2018; 192:199-225. [PMID: 30453216 DOI: 10.1016/j.biomaterials.2018.11.014] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Revised: 11/02/2018] [Accepted: 11/09/2018] [Indexed: 12/27/2022]
Abstract
The choice of the best-suited cell population for the regeneration of damaged or diseased cartilage depends on the effectiveness of culture conditions (e.g. media supplements, three-dimensional scaffolds, mechanical stimulation, oxygen tension, co-culture systems) to induce stable chondrogenic phenotype. Herein, advances and shortfalls in in vitro, preclinical and clinical setting of various in vitro microenvironment modulators on maintaining chondrocyte phenotype or directing stem cells towards chondrogenic lineage are critically discussed. Chondrocytes possess low isolation efficiency, limited proliferative potential and rapid phenotypic drift in culture. Mesenchymal stem cells are relatively readily available, possess high proliferation potential, exhibit great chondrogenic differentiation capacity, but they tend to acquire a hypertrophic phenotype when exposed to chondrogenic stimuli. Embryonic and induced pluripotent stem cells, despite their promising in vitro and preclinical data, are still under-investigated. Although a stable chondrogenic phenotype remains elusive, recent advances in in vitro microenvironment modulators are likely to develop clinically- and commercially-relevant therapies in the years to come.
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Affiliation(s)
- Valeria Graceffa
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland
| | - Claire Vinatier
- INSERMU1229, Regenerative Medicine and Skeleton (RMeS), University of Nantes, UFR Odontologie & CHU Nantes, PHU 4 OTONN, 44042 Nantes, France
| | - Jerome Guicheux
- INSERMU1229, Regenerative Medicine and Skeleton (RMeS), University of Nantes, UFR Odontologie & CHU Nantes, PHU 4 OTONN, 44042 Nantes, France
| | - Martin Stoddart
- AO Research Institute, Clavadelerstrasse 8, 7270 Davos, Switzerland
| | - Mauro Alini
- AO Research Institute, Clavadelerstrasse 8, 7270 Davos, Switzerland
| | - Dimitrios I Zeugolis
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland.
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Ma C, Wang K, Ji H, Wang H, Guo L, Wang Z, Ren H, Wang X, Guan W. Multilineage potential research of Beijing duck amniotic mesenchymal stem cells. Cell Tissue Bank 2018; 19:519-529. [PMID: 29858719 PMCID: PMC6280870 DOI: 10.1007/s10561-018-9701-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Accepted: 05/14/2018] [Indexed: 12/18/2022]
Abstract
Amnion, which is usually discarded as medical waste, is considered as abundant sources for mesenchymal stem cells. In human and veterinary medicine, the multipotency of mesenchymal stem cells derived from amnion (AMSCs) together with their plasticity, self-renewal, low immunogenicity and nontumorigenicity characteristics make AMSCs a promising candidate cell for cell-based therapies and tissue engineering. However, up till now, the multipotential characteristics and therapeutic potential of AMSCs on preclinical studies remain uncertain. In this work, we successfully obtained AMSCs from Beijing duck embryos in vitro, and also attempted to detect their biological characteristics. The isolated AMSCs were phenotypically identified, the growth kinetics and karyotype were tested. Also, the cells were positive for MSCs-related markers (CD29, CD71, CD105, CD166, Vimentin and Fibronection), while the expression of CD34 and CD45 were undetectable. Additionally, AMSCs also expressed the pluripotent marker gene OCT4. Particularly, when appropriately induced, AMSCs could be induced to trans-differentiate into adipocytes, osteoblasts, chondrocytes and neurocytes in vitro. Together, these results demonstrated that the isolated AMSCs maintained their stemness and proliferation in vitro, which may be useful for future cell therapy in regenerative medicine.
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Affiliation(s)
- Caiyun Ma
- Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Kunfu Wang
- College of Wildlife Resources, Northeast Forestry University, Harbin, China
| | - Hongda Ji
- Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Hongliang Wang
- Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Liangcai Guo
- Mudanjiang Normal University, Mudanjiang, 157011, China
| | - Zhiyong Wang
- Mudanjiang Normal University, Mudanjiang, 157011, China
| | - Han Ren
- Mudanjiang Normal University, Mudanjiang, 157011, China
| | - Xishuai Wang
- Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Weijun Guan
- Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
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Li B, Zhang Y, Li M, Zhao X, Xie H, Guo X, Wang F, Xia H, Chen B. Genetic correction of adipose tissue-derived mesenchymal stem cells mediated by TALEN targeting the GDF5 gene. Int J Mol Med 2018; 41:2397-2405. [PMID: 29393424 DOI: 10.3892/ijmm.2018.3442] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Accepted: 10/04/2017] [Indexed: 11/06/2022] Open
Abstract
Stem cells and other associated cell types may be a potential alternative to treat various genetic disorders that currently do not benefit from traditional approaches. Functional recovery of cells could be induced via directional differentiation or genetic manipulation. In this study, mesenchymal stem cells (MSCs) were obtained from a patient with osteoarthritis (OA) carrying a functional single‑nucleotide polymorphism (SNP rs143383, C/T transition) within the 5'‑UTR of growth and differentiation factor 5 (GDF5) gene. The SNP causes GDF5 expression to be reduced and thus increases OA susceptibility. Aiming to correct the dysfunctional gene, a pair of transcription activator‑like effector nucleases (TALENs) were designed to cleave the DNA around the mutated locus, coupled with a short single stranded DNA complementary to the cleavage site. Following in vitro cell colony formation and selection, two genetically corrected MSC colonies were identified out of a total of 142. These MSCs were induced and differentiated into chondrocytes. As a result, genetically corrected chondrocytes exhibited normal morphology and lower levels of apoptosis compared with cells carrying the SNP. In cultured cells, the secretion of matrix metalloproteinases was suppressed and TIMP metallopeptidase inhibitor 1 was increased by correction of the mutation. Furthermore, the expression of GDF5 target genes, cell vitality‑associated genes and extracellular matrix degrading genes were returned to normal levels in corrected cells compared with mutation‑carrying cells, indicating the functional recovery of these corrected chondrocytes. The present study demonstrated that TALEN‑mediated genetic correction can be used to edit genes in adipose‑derived MSCs from patients with OA and may have clinical potential.
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Affiliation(s)
- Baofeng Li
- Department of Orthopaedics, Guangzhou General Hospital of Guangzhou Military Command, Institute of Traumatic Orthopaedics of PLA, Guangzhou, Guangdong 510010, P.R. China
| | - Ying Zhang
- Department of Orthopaedics, Guangzhou General Hospital of Guangzhou Military Command, Institute of Traumatic Orthopaedics of PLA, Guangzhou, Guangdong 510010, P.R. China
| | - Mei Li
- Department of Orthopaedics, Guangzhou General Hospital of Guangzhou Military Command, Institute of Traumatic Orthopaedics of PLA, Guangzhou, Guangdong 510010, P.R. China
| | - Xiaoliang Zhao
- Department of Orthopaedics, Guangzhou General Hospital of Guangzhou Military Command, Institute of Traumatic Orthopaedics of PLA, Guangzhou, Guangdong 510010, P.R. China
| | - Huibin Xie
- Department of Orthopaedics, Guangzhou General Hospital of Guangzhou Military Command, Institute of Traumatic Orthopaedics of PLA, Guangzhou, Guangdong 510010, P.R. China
| | - Xiaoze Guo
- Department of Orthopaedics, Guangzhou General Hospital of Guangzhou Military Command, Institute of Traumatic Orthopaedics of PLA, Guangzhou, Guangdong 510010, P.R. China
| | - Fei Wang
- Department of Orthopaedics, Guangzhou General Hospital of Guangzhou Military Command, Institute of Traumatic Orthopaedics of PLA, Guangzhou, Guangdong 510010, P.R. China
| | - Hong Xia
- Department of Orthopaedics, Guangzhou General Hospital of Guangzhou Military Command, Institute of Traumatic Orthopaedics of PLA, Guangzhou, Guangdong 510010, P.R. China
| | - Bei Chen
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
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Beeravolu N, Brougham J, Khan I, McKee C, Perez-Cruet M, Chaudhry GR. Human umbilical cord derivatives regenerate intervertebral disc. J Tissue Eng Regen Med 2018; 12:e579-e591. [PMID: 27690334 DOI: 10.1002/term.2330] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2016] [Revised: 08/03/2016] [Accepted: 09/26/2016] [Indexed: 09/11/2024]
Abstract
Intervertebral disc (IVD) degeneration is characterized by the loss of nucleus pulposus (NP), which is a common cause for lower back pain. Although, currently, there is no cure for the degenerative disc disease, stem cell therapy is increasingly being considered for its treatment. In this study, we investigated the feasibility and efficacy of human umbilical cord mesenchymal stem cells (MSCs) and chondroprogenitor cells (CPCs) derived from those cells to regenerate damaged IVD in a rabbit model. Transplanted cells survived, engrafted and dispersed into NP in situ. Significant improvement in the histology, cellularity, extracellular matrix proteins, and water and glycosaminoglycan contents in IVD recipients of CPCs was observed compared to MSCs. In addition, IVDs receiving CPCs exhibited higher expression of NP-specific human markers, SOX9, aggrecan, collagen 2, FOXF1 and KRT19. The novelty of the study is that in vitro differentiated CPCs derived from umbilical cord MSCs, demonstrated far greater capacity to regenerate damaged IVDs, which provides basis and impetus for stem cell based clinical studies to treat degenerative disc disease. Copyright © 2016 John Wiley & Sons, Ltd.
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Affiliation(s)
- Naimisha Beeravolu
- Department of Biological Sciences, Oakland University, Rochester, Michigan, USA
- OUWB Institute for Stem Cell and Regenerative Medicine, Rochester, Michigan, USA
| | - Jared Brougham
- OUWB School of Medicine, Oakland University, Rochester, Michigan, USA
| | - Irfan Khan
- Department of Biological Sciences, Oakland University, Rochester, Michigan, USA
- OUWB Institute for Stem Cell and Regenerative Medicine, Rochester, Michigan, USA
- Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
| | - Christina McKee
- Department of Biological Sciences, Oakland University, Rochester, Michigan, USA
- OUWB Institute for Stem Cell and Regenerative Medicine, Rochester, Michigan, USA
| | - Mick Perez-Cruet
- OUWB Institute for Stem Cell and Regenerative Medicine, Rochester, Michigan, USA
- Beaumont Health System, Royal Oak, Michigan, USA
| | - G Rasul Chaudhry
- Department of Biological Sciences, Oakland University, Rochester, Michigan, USA
- OUWB Institute for Stem Cell and Regenerative Medicine, Rochester, Michigan, USA
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Park YB, Ha CW, Kim JA, Rhim JH, Park YG, Chung JY, Lee HJ. Effect of Transplanting Various Concentrations of a Composite of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronic Acid Hydrogel on Articular Cartilage Repair in a Rabbit Model. PLoS One 2016; 11:e0165446. [PMID: 27824874 PMCID: PMC5100912 DOI: 10.1371/journal.pone.0165446] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2016] [Accepted: 10/12/2016] [Indexed: 02/06/2023] Open
Abstract
Background Mesenchymal stem cells (MSCs) are known to have therapeutic potential for cartilage repair. However, the optimal concentration of MSCs for cartilage repair remains unclear. Therefore, we aimed to explore the feasibility of cartilage repair by human umbilical cord blood-derived MSCs (hUCB-MSCs) and to determine the optimal concentrations of the MSCs in a rabbit model. Methods Osteochondral defects were created in the trochlear groove of femur in 55 rabbits. Four experimental groups (11 rabbits/group) were treated by transplanting the composite of hUCB-MSCs and HA with various MSCs concentrations (0.1, 0.5, 1.0, and 1.5 x 107 cells/ml). One control group was left untreated. At 4, 8, and 16 weeks post-transplantation, the degree of cartilage repair was evaluated grossly and histologically. Findings Overall, transplanting hUCB-MSCs and HA hydrogel resulted in cartilage repair tissue with better quality than the control without transplantation (P = 0.015 in 0.1, P = 0.004 in 0.5, P = 0.004 in 1.0, P = 0.132 in 1.5 x 107 cells/ml). Interestingly, high cell concentration of hUCB-MSCs (1.5×107 cells/ml) was inferior to low cell concentrations (0.1, 0.5, and 1.0 x 107 cells/ml) in cartilage repair (P = 0.394,P = 0.041, P = 0.699, respectively). The 0.5 x 107 cells/ml group showed the highest cartilage repair score at 4, 8 and 16 weeks post transplantation, and followed by 0.1x107 cells/ml group or 1.0 x 107 cell/ml group. Conclusions The results of this study suggest that transplantation of the composite of hUCB-MSCs and HA is beneficial for cartilage repair. In addition, this study shows that optimal MSC concentration needs to be determined for better cartilage repair.
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Affiliation(s)
- Yong-Beom Park
- Department of Orthopedic Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul 06973, South Korea
| | - Chul-Won Ha
- Department of Orthopaedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, South Korea
- Stem Cell & Regenerative Medicine Research Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, South Korea
- Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea
- * E-mail: ,
| | - Jin-A Kim
- Department of Orthopaedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, South Korea
- Stem Cell & Regenerative Medicine Research Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, South Korea
| | - Ji-Heon Rhim
- Department of Orthopaedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, South Korea
- Stem Cell & Regenerative Medicine Research Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, South Korea
| | - Yong-Geun Park
- Department of Orthopedic Surgery, Jeju National University Hospital, Jeju National University School of Medicine, 15 Aran 13-gil, Jeju-si 63241, South Korea
| | - Jun Young Chung
- Department of Orthopaedic Surgery, Ajou University Hospital, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, South Korea
| | - Han-Jun Lee
- Department of Orthopedic Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul 06973, South Korea
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Frisch J, Cucchiarini M. Gene- and Stem Cell-Based Approaches to Regulate Hypertrophic Differentiation in Articular Cartilage Disorders. Stem Cells Dev 2016; 25:1495-1512. [DOI: 10.1089/scd.2016.0106] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Affiliation(s)
- Janina Frisch
- Center of Experimental Orthopaedics, Saarland University and Saarland University Medical Center, Homburg, Germany
| | - Magali Cucchiarini
- Center of Experimental Orthopaedics, Saarland University and Saarland University Medical Center, Homburg, Germany
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