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Mazzoni E, Iaquinta MR, Mosaico M, De Pace R, D'Agostino A, Tognon M, Martini F. Human Mesenchymal Stem Cells and Innovative Scaffolds for Bone Tissue Engineering Applications. TISSUE ENGINEERING. PART B, REVIEWS 2023; 29:514-531. [PMID: 37212264 DOI: 10.1089/ten.teb.2022.0217] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
Stem cell-based therapy is a significant topic in regenerative medicine, with a predominant role being played by human mesenchymal stem cells (hMSCs). The hMSCs have been shown to be suitable in regenerative medicine for the treatment of bone tissue. In the last few years, the average lifespan of our population has gradually increased. The need of biocompatible materials, which exhibit high performances, such as efficiency in bone regeneration, has been highlighted by aging. Current studies emphasize the benefit of using biomimetic biomaterials, also known as scaffolds, for bone grafts to speed up bone repair at the fracture site. For the healing of injured bone and bone regeneration, regenerative medicine techniques utilizing a combination of these biomaterials, together with cells and bioactive substances, have drawn a great interest. Cell therapy, based on the use of hMSCs, alongside materials for the healing of damaged bone, has obtained promising results. In this work, several aspects of cell biology, tissue engineering, and biomaterials applied to bone healing/regrowth will be considered. In addition, the role of hMSCs in these fields and recent progress in clinical applications are discussed. Impact Statement The restoration of large bone defects is both a challenging clinical issue and a socioeconomic problem on a global scale. Different therapeutic approaches have been proposed for human mesenchymal stem cells (hMSCs), considering their paracrine effect and potential differentiation into osteoblasts. However, different limitations are still to be overcome in using hMSCs as a therapeutic opportunity in bone fracture repair, including hMSC administration methods. To identify a suitable hMSC delivery system, new strategies have been proposed using innovative biomaterials. This review provides an update of the literature on hMSC/scaffold clinical applications for the management of bone fractures.
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Affiliation(s)
- Elisa Mazzoni
- Department of Chemical, Pharmaceutical and Agricultural Sciences, and University of Ferrara, Ferrara, Italy
| | - Maria Rosa Iaquinta
- Department of Medical Sciences, University of Ferrara, Ferrara, Italy
- Dentistry and Maxillo-Facial Surgery Unit, Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, Verona, Italy
| | - Maria Mosaico
- Department of Medical Sciences, University of Ferrara, Ferrara, Italy
| | - Raffaella De Pace
- Department of Medical Sciences, University of Ferrara, Ferrara, Italy
| | - Antonio D'Agostino
- Dentistry and Maxillo-Facial Surgery Unit, Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, Verona, Italy
| | - Mauro Tognon
- Department of Medical Sciences, University of Ferrara, Ferrara, Italy
| | - Fernanda Martini
- Department of Medical Sciences, University of Ferrara, Ferrara, Italy
- Laboratory for Technologies of Advanced Therapies, University of Ferrara, Ferrara, Italy
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Richter RF, Vater C, Korn M, Ahlfeld T, Rauner M, Pradel W, Stadlinger B, Gelinsky M, Lode A, Korn P. Treatment of critical bone defects using calcium phosphate cement and mesoporous bioactive glass providing spatiotemporal drug delivery. Bioact Mater 2023; 28:402-419. [PMID: 37361564 PMCID: PMC10285454 DOI: 10.1016/j.bioactmat.2023.06.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 05/22/2023] [Accepted: 06/01/2023] [Indexed: 06/28/2023] Open
Abstract
Calcium phosphate cements (CPC) are currently widely used bone replacement materials with excellent bioactivity, but have considerable disadvantages like slow degradation. For critical-sized defects, however, an improved degradation is essential to match the tissue regeneration, especially in younger patients who are still growing. We demonstrate that a combination of CPC with mesoporous bioactive glass (MBG) particles led to an enhanced degradation in vitro and in a critical alveolar cleft defect in rats. Additionally, to support new bone formation the MBG was functionalized with hypoxia conditioned medium (HCM) derived from rat bone marrow stromal cells. HCM-functionalized scaffolds showed an improved cell proliferation and the highest formation of new bone volume. This highly flexible material system together with the drug delivery capacity is adaptable to patient specific needs and has great potential for clinical translation.
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Affiliation(s)
- Richard Frank Richter
- Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany
| | - Corina Vater
- Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany
| | - Margarete Korn
- Department of Oral and Maxillofacial Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
| | - Tilman Ahlfeld
- Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany
| | - Martina Rauner
- Department of Medicine III and Center for Healthy Aging, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
| | - Winnie Pradel
- Department of Oral and Maxillofacial Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
| | - Bernd Stadlinger
- Clinic of Cranio-Maxillofacial and Oral Surgery, Center of Dental Medicine, University of Zurich, Switzerland
| | - Michael Gelinsky
- Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany
| | - Anja Lode
- Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany
| | - Paula Korn
- Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany
- Department of Oral and Maxillofacial Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
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Mendiratta M, Mendiratta M, Mohanty S, Sahoo RK, Prakash H. Breaking the graft-versus-host-disease barrier: Mesenchymal stromal/stem cells as precision healers. Int Rev Immunol 2023; 43:95-112. [PMID: 37639700 DOI: 10.1080/08830185.2023.2252007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 08/08/2023] [Accepted: 08/21/2023] [Indexed: 08/31/2023]
Abstract
Mesenchymal Stromal/Stem Cells (MSCs) are multipotent, non-hematopoietic progenitor cells with a wide range of immune modulation and regenerative potential which qualify them as a potential component of cell-based therapy for various autoimmune/chronic inflammatory ailments. Their immunomodulatory properties include the secretion of immunosuppressive cytokines, the ability to suppress T-cell activation and differentiation, and the induction of regulatory T-cells. Considering this and our interest, we here discuss the significance of MSC for the management of Graft-versus-Host-Disease (GvHD), one of the autoimmune manifestations in human. In pre-clinical models, MSCs have been shown to reduce the severity of GvHD symptoms, including skin and gut damage, which are the most common and debilitating manifestations of this disease. While initial clinical studies of MSCs in GvHD cases were promising, the results were variable in randomized studies. So, further studies are warranted to fully understand their potential benefits, safety profile, and optimal dosing regimens. Owing to these inevitable issues, here we discuss various mechanisms, and how MSCs can be employed in managing GvHD, as a cellular therapeutic approach for this disease.
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Affiliation(s)
- Mohini Mendiratta
- Department of Medical Oncology, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
| | | | - Sujata Mohanty
- Stem Cell Facility, All India Institute of Medical Sciences, New Delhi, India
| | - Ranjit Kumar Sahoo
- Department of Medical Oncology, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
| | - Hridayesh Prakash
- Amity Centre for Translational Research, Amity University, Noida, India
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Zhu X, Wang C, Bai H, Zhang J, Wang Z, Li Z, Zhao X, Wang J, Liu H. Functionalization of biomimetic mineralized collagen for bone tissue engineering. Mater Today Bio 2023; 20:100660. [PMID: 37214545 PMCID: PMC10199226 DOI: 10.1016/j.mtbio.2023.100660] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 04/18/2023] [Accepted: 05/04/2023] [Indexed: 05/24/2023] Open
Abstract
Mineralized collagen (MC) is the basic unit of bone structure and function and is the main component of the extracellular matrix (ECM) in bone tissue. In the biomimetic method, MC with different nanostructures of neo-bone have been constructed. Among these, extra-fibrous MC has been approved by regulatory agencies and applied in clinical practice to play an active role in bone defect repair. However, in the complex microenvironment of bone defects, such as in blood supply disorders and infections, MC is unable to effectively perform its pro-osteogenic activities and needs to be functionalized to include osteogenesis and the enhancement of angiogenesis, anti-infection, and immunomodulation. This article aimed to discuss the preparation and biological performance of MC with different nanostructures in detail, and summarize its functionalization strategy. Then we describe the recent advances in the osteo-inductive properties and multifunctional coordination of MC. Finally, the latest research progress of functionalized biomimetic MC, along with the development challenges and future trends, are discussed. This paper provides a theoretical basis and advanced design philosophy for bone tissue engineering in different bone microenvironments.
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Affiliation(s)
- Xiujie Zhu
- Department of Orthopedics, The Second Hospital of Jilin University, 4110 Yatai Street, Changchun, 130041, PR China
| | - Chenyu Wang
- Department of Plastic and Reconstruct Surgery, The First Hospital of Jilin University, 1 Xinmin Street, Changchun, 130021, PR China
| | - Haotian Bai
- Department of Orthopedics, The Second Hospital of Jilin University, 4110 Yatai Street, Changchun, 130041, PR China
| | - Jiaxin Zhang
- Department of Orthopedics, The Second Hospital of Jilin University, 4110 Yatai Street, Changchun, 130041, PR China
| | - Zhonghan Wang
- Department of Orthopedics, The Second Hospital of Jilin University, 4110 Yatai Street, Changchun, 130041, PR China
| | - Zuhao Li
- Department of Orthopedics, The Second Hospital of Jilin University, 4110 Yatai Street, Changchun, 130041, PR China
| | - Xin Zhao
- Department of Orthopedics, The Second Hospital of Jilin University, 4110 Yatai Street, Changchun, 130041, PR China
| | - Jincheng Wang
- Department of Orthopedics, The Second Hospital of Jilin University, 4110 Yatai Street, Changchun, 130041, PR China
| | - He Liu
- Department of Orthopedics, The Second Hospital of Jilin University, 4110 Yatai Street, Changchun, 130041, PR China
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Combined application of BMP-2 and naturally occurring bioactive factor mixtures for the optimized therapy of segmental bone defects. Acta Biomater 2023; 157:162-174. [PMID: 36481501 DOI: 10.1016/j.actbio.2022.11.064] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 11/27/2022] [Accepted: 11/30/2022] [Indexed: 12/12/2022]
Abstract
Critical bone defects are the result of traumatic, infection- or tumor-induced segmental bone loss and represent a therapeutic problem that has not been solved by current reconstructive or regenerative strategies yet. Scaffolds functionalized with naturally occurring bioactive factor mixtures show a promising chemotactic and angiogenic potential in vitro and therefore might stimulate bone regeneration in vivo. To assess this prospect, the study targets at heparin-modified mineralized collagen scaffolds functionalized with naturally occurring bioactive factor mixtures and/or rhBMP-2. These scaffolds were implanted into a 2-mm segmental femoral defect in mice and analyzed in respect to newly formed bone volume (BV) and bone mineral density (BMD) by micro-computed tomography scans after an observation period of 6 weeks. To rate the degree of defect healing, the number of vessels, and the activity of osteoclasts and osteoblasts were analyzed histologically. The sole application of bioactive factor mixtures is inferior to the use of the recombinant growth factor rhBMP-2 regarding BV and degree of defect healing. A higher rhBMP-2 concentration or the combination with bioactive factor mixtures does not lead to a further enhancement in defect healing. Possibly, a synergistic effect can be achieved by further concentration or a prolonged release of bioactive factor mixtures. STATEMENT OF SIGNIFICANCE: The successful therapy of extended bone defects is still a major challenge in clinical routine. In this study we investigated the bone regenerative potential of naturally occuring bioactive factor mixtures derived from platelet concentrates, adipose tissue and cell secretomes as a cheap and promising alternative to recombinant growth factors in a murine segmental bone defect model. The mixtures alone were not able to induce complete bridging of the bone defect, but in combination with bone morphogenetic protein 2 bone healing seemed to be more physiological. The results show that naturally occuring bioactive factor mixtures are a promising add-on in a clinical setting.
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Shi MY, Liu L, Yang FY. Strategies to improve the effect of mesenchymal stem cell therapy on inflammatory bowel disease. World J Stem Cells 2022; 14:684-699. [PMID: 36188115 PMCID: PMC9516464 DOI: 10.4252/wjsc.v14.i9.684] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 07/07/2022] [Accepted: 09/07/2022] [Indexed: 02/07/2023] Open
Abstract
Inflammatory bowel disease (IBD) includes Crohn’s disease and ulcerative colitis and is an idiopathic, chronic inflammatory disease of the colonic mucosa. The occurrence of IBD, causes irreversible damage to the colon and increases the risk of carcinoma. The routine clinical treatment of IBD includes drug treatment, endoscopic treatment and surgery. The vast majority of patients are treated with drugs and biological agents, but the complete cure of IBD is difficult. Mesenchymal stem cells (MSCs) have become a new type of cell therapy for the treatment of IBD due to their immunomodulatory and nutritional functions, which have been confirmed in many clinical trials. This review discusses some potential mechanisms of MSCs in the treatment of IBD, summarizes the experimental results, and provides new insights to enhance the therapeutic effects of MSCs in future applications.
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Affiliation(s)
- Meng-Yue Shi
- School of Medicine, Yangtze University, Jingzhou 434023, Hubei Province, China
| | - Lian Liu
- Department of Pharmacology, Medical School of Yangtze University, Yangtze University, Jingzhou 434023, Hubei Province, China
| | - Fu-Yuan Yang
- Health Science Center, Yangtze University, Jingzhou 434020, Hubei Province, China
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Sarsenova M, Kim Y, Raziyeva K, Kazybay B, Ogay V, Saparov A. Recent advances to enhance the immunomodulatory potential of mesenchymal stem cells. Front Immunol 2022; 13:1010399. [PMID: 36211399 PMCID: PMC9537745 DOI: 10.3389/fimmu.2022.1010399] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Accepted: 09/07/2022] [Indexed: 11/19/2022] Open
Abstract
Considering the unique therapeutic potential of mesenchymal stem cells (MSCs), including their immunosuppressive and immunomodulatory properties as well as their ability to improve tissue regeneration, these cells have attracted the attention of scientists and clinicians for the treatment of different inflammatory and immune system mediated disorders. However, various clinical trials using MSCs for the therapeutic purpose are conflicting and differ from the results of promising preclinical studies. This inconsistency is caused by several factors such as poor migration and homing capacities, low survival rate, low level of proliferation and differentiation, and donor-dependent variation of the cells. Enhancement and retention of persistent therapeutic effects of the cells remain a challenge to overcome in MSC-based therapy. In this review, we summarized various approaches to enhance the clinical outcomes of MSC-based therapy as well as revised current and future perspectives for the creation of cellular products with improved potential for diverse clinical applications.
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Affiliation(s)
- Madina Sarsenova
- Department of Medicine, School of Medicine, Nazarbayev University, Nur-Sultan, Kazakhstan
| | - Yevgeniy Kim
- Department of Medicine, School of Medicine, Nazarbayev University, Nur-Sultan, Kazakhstan
| | - Kamila Raziyeva
- Department of Medicine, School of Medicine, Nazarbayev University, Nur-Sultan, Kazakhstan
| | - Bexultan Kazybay
- Department of Medicine, School of Medicine, Nazarbayev University, Nur-Sultan, Kazakhstan
| | - Vyacheslav Ogay
- Laboratory of Stem Cells, National Center for Biotechnology, Nur-Sultan, Kazakhstan
| | - Arman Saparov
- Department of Medicine, School of Medicine, Nazarbayev University, Nur-Sultan, Kazakhstan
- *Correspondence: Arman Saparov,
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Zhang W, Hu J, Huang Y, Wu C, Xie H. Urine-derived stem cells: applications in skin, bone and articular cartilage repair. BURNS & TRAUMA 2021; 9:tkab039. [PMID: 34859109 PMCID: PMC8633594 DOI: 10.1093/burnst/tkab039] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 09/18/2021] [Indexed: 02/05/2023]
Abstract
As an emerging type of adult stem cell featuring non-invasive acquisition, urine-derived stem cells (USCs) have shown great potential for applications in tissue engineering and regenerative medicine. With a growing amount of research on the topic, the effectiveness of USCs in various disease models has been shown and the underlying mechanisms have also been explored, though many aspects still remain unclear. In this review, we aim to provide an up-to-date overview of the biological characteristics of USCs and their applications in skin, bone and articular cartilage repair. In addition to the identification procedure of USCs, we also summarize current knowledge of the underlying repair mechanisms and application modes of USCs. Potential concerns and perspectives have also been summarized.
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Affiliation(s)
- Wenqian Zhang
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Jungen Hu
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yizhou Huang
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Chenyu Wu
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Huiqi Xie
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
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Zhang J, Qin X, Deng Y, Lu J, Li Z, Feng Y, Yan X, Chen M, Gao L, Xu Y, Shi D, Lu F. Transforming Growth Factor-β1 Enhances Mesenchymal Characteristics of Buffalo ( Bubalus bubalis) Bone Marrow-Derived Mesenchymal Stem Cells. Cell Reprogram 2021; 23:127-138. [PMID: 33861638 DOI: 10.1089/cell.2020.0093] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Bone marrow-derived mesenchymal stem cells (BMSCs) from livestock are valuable resources for animal reproduction and veterinary therapeutics. Previous studies have shown that BMSCs were prone to malignant transformation of mesenchymal-to-epithelial transition in vitro, which can cause many barriers to further application of BMSCs. The transforming growth factor β (TGF-β) signaling pathway has been widely studied as the most important signaling pathway involved in regulating mesenchymal features of BMSCs. However, the effects of the TGF-β signaling pathway on mesenchymal characteristics of buffalo BMSCs (bBMSCs) remain unclear. In the present study, the impacts of the growth factor, TGF-β1, on cell proliferation, apoptosis, migration, and karyotype of bBMSCs were tested. Besides, the effects of TGF-β1 on pluripotency, mesenchymal markers, and epithelial-to-mesenchymal transition (EMT)-related gene expression of bBMSCs were also examined. Results showed that the suitable concentration and time of TGF-β1 treatment (2 ng/mL and 24 hours) promoted cell proliferation and significantly reduced cell apoptosis (p < 0.05) in bBMSCs. The cell migration capacity and normal karyotype rate of bBMSCs were significantly (p < 0.05) improved under TGF-β1 treatment. The expression levels of pluripotency-related genes (Sox2 and Nanog) and mesenchymal markers (N-cadherin and Fn1) were significantly (p < 0.05) up-regulated under TGF-β1 treatment. Furthermore, TGF-β1 activated the EMT process, thereby contributing to significantly enhancing the expression levels of EMT-related genes (Snail and Slug) (p < 0.05), which in turn improved maintenance of the mesenchymal nature in bBMSCs. Finally, bBMSCs underwent self-transformation more easily and efficiently and exhibited more characteristics of mesenchymal stem cells under TGF-β1 treatment. This study provides theoretical guidance for elucidating the detailed mechanism of the TGF-β signaling pathway in mesenchymal feature maintenance of bBMSCs and is of significance to establish a stable culture system of bBMSCs.
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Affiliation(s)
- Jun Zhang
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
| | - Xiling Qin
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
| | - Yanfei Deng
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
| | - Jiaka Lu
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
| | - Zhengda Li
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
| | - Yun Feng
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
| | - Xi Yan
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
| | - Mengjia Chen
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
| | - Lv Gao
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
| | - Ye Xu
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
| | - Deshun Shi
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
| | - Fenghua Lu
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
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Mesenchymal stem cell-derived secretomes for therapeutic potential of premature infant diseases. Biosci Rep 2021; 40:222738. [PMID: 32320046 PMCID: PMC7953482 DOI: 10.1042/bsr20200241] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 04/20/2020] [Accepted: 04/21/2020] [Indexed: 02/06/2023] Open
Abstract
Preterm birth is a complex syndrome and remains a substantial public health problem globally. Its common complications include periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP). Despite great advances in the comprehension of the pathogenesis and improvements in neonatal intensive care and associated medicine, preterm birth-related diseases remain essentially without adequate treatment and can lead to high morbidity and mortality. The therapeutic potential of mesenchymal stem/stromal cells (MSCs) appears promising as evidenced by their efficacy in preclinical models of pathologies relevant to premature infant complications. MSC-based therapeutic efficacy is closely associated with MSC secretomes and a subsequent paracrine action response to tissue injuries, which are complex and abundant in response to the local microenvironment. In the current review, we summarize the paracrine mechanisms of MSC secretomes underlying diverse preterm birth-related diseases, including PVL, BPD, NEC and ROP, are summarized, and focus is placed on MSC-conditioned media (CM) and MSC-derived extracellular vesicles (EVs) as key mediators of modulatory action, thereby providing new insights for future therapies in newborn medicine.
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Couto de Carvalho LA, Tosta Dos Santos SL, Sacramento LV, de Almeida VR, de Aquino Xavier FC, Dos Santos JN, Gomes Henriques Leitão ÁC. Mesenchymal stem cell markers in periodontal tissues and periapical lesions. Acta Histochem 2020; 122:151636. [PMID: 33132168 DOI: 10.1016/j.acthis.2020.151636] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Revised: 09/28/2020] [Accepted: 10/04/2020] [Indexed: 12/26/2022]
Abstract
INTRODUCTION Mesenchymal stem cells (MSCs) are characterized by the potential to differentiate into multiple cell lineages, high proliferation rates, and self-renewal capacity, in addition to the ability to maintain their undifferentiated state. These cells have been identified in physiological oral tissues such as pulp tissue, dental follicle, apical papilla and periodontal ligament, as well as in pathological situations such as chronic periapical lesions (CPLs). The criteria used for the identification of MSCs include the positive expression of specific surface antigens, with CD73, CD90, CD105, CD44, CD146, STRO-1, CD166, NANOG and OCT4 being the most specific for these cells. AIM The aim of this review was to explore the literature on markers able to identify MSCs as well as the presence of these cells in the healthy periodontal ligament and CPLs, highlighting their role in regenerative medicine and implications in the progression of these lesions. METHODS Narrative literature review searching the PubMed and Medline databases. Articles published in English between 1974 and 2020 were retrieved. CONCLUSION The included studies confirmed the presence of MSCs in the healthy periodontal ligament and in CPLs. Several surface markers are used for the characterization of these cells which, although not specific, are effective in cell recognition. Mesenchymal stem cells participate in tissue repair, exerting anti- inflammatory, immunosuppressive and proangiogenic effects, and are therefore involved in the progression and attenuation of CPLs or even in the persistence of these lesions.
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Affiliation(s)
| | | | | | | | | | - Jean Nunes Dos Santos
- Postgraduation Program in Dentistry and Health, Federal University of Bahia, Salvador, BA, Brazil
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Wang Y, Bian Y, Zhou L, Feng B, Weng X, Liang R. Biological evaluation of bone substitute. Clin Chim Acta 2020; 510:544-555. [PMID: 32798511 DOI: 10.1016/j.cca.2020.08.017] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 08/09/2020] [Accepted: 08/10/2020] [Indexed: 01/02/2023]
Abstract
Critical-sized defects (CSDs) caused by trauma, tumor resection, or skeletal abnormalities create a high demand for bone repair materials (BRMs). Over the years, scientists have been trying to develop BRMs and evaluate their efficacy using numerous developed methods. BRMs are characterized by osteogenesis and angiogenesis promoting properties, the latter of which has rarely been studied in vitro and in vivo. While blood vessels are required to provide nutrients. Bone mass maintains a dynamic balance under the joint action of osteolytic and osteogenic activity in which monocytes differentiate into osteolytic cells, and osteoprogenitor cells differentiate into osteogenic cells. This review would be helpful for inexperienced researchers as well as present a comprehensive overview of methods used to investigate the effect of BRMs on osteogenic cells, osteolytic cells, and blood vessels, as well as their biocompatibility and biological performance. This review is expected to facilitate further research and development of new BRMs.
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Affiliation(s)
- Yingjie Wang
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Yanyan Bian
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Lizhi Zhou
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Bin Feng
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.
| | - Xisheng Weng
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.
| | - Ruizheng Liang
- State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
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13
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Goodman SB, Lin T. Modifying MSC Phenotype to Facilitate Bone Healing: Biological Approaches. Front Bioeng Biotechnol 2020; 8:641. [PMID: 32671040 PMCID: PMC7328340 DOI: 10.3389/fbioe.2020.00641] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 05/26/2020] [Indexed: 12/11/2022] Open
Abstract
Healing of fractures and bone defects normally follows an orderly series of events including formation of a hematoma and an initial stage of inflammation, development of soft callus, formation of hard callus, and finally the stage of bone remodeling. In cases of severe musculoskeletal injury due to trauma, infection, irradiation and other adverse stimuli, deficient healing may lead to delayed or non-union; this results in a residual bone defect with instability, pain and loss of function. Modern methods of mechanical stabilization and autologous bone grafting are often successful in achieving fracture union and healing of bone defects; however, in some cases, this treatment is unsuccessful because of inadequate biological factors. Specifically, the systemic and local microenvironment may not be conducive to bone healing because of a loss of the progenitor cell population for bone and vascular lineage cells. Autologous bone grafting can provide the necessary scaffold, progenitor and differentiated lineage cells, and biological cues for bone reconstruction, however, autologous bone graft may be limited in quantity or quality. These unfavorable circumstances are magnified in systemic conditions with chronic inflammation, including obesity, diabetes, chronic renal disease, aging and others. Recently, strategies have been devised to both mitigate the necessity for, and complications from, open procedures for harvesting of autologous bone by using minimally invasive aspiration techniques and concentration of iliac crest bone cells, followed by local injection into the defect site. More elaborate strategies (not yet approved by the U.S. Food and Drug Administration-FDA) include isolation and expansion of subpopulations of the harvested cells, preconditioning of these cells or inserting specific genes to modulate or facilitate bone healing. We review the literature pertinent to the subject of modifying autologous harvested cells including MSCs to facilitate bone healing. Although many of these techniques and technologies are still in the preclinical stage and not yet approved for use in humans by the FDA, novel approaches to accelerate bone healing by modifying cells has great potential to mitigate the physical, economic and social burden of non-healing fractures and bone defects.
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Affiliation(s)
- Stuart B Goodman
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Redwood City, CA, United States.,Department of Bioengineering, Stanford University, Stanford, CA, United States
| | - Tzuhua Lin
- Orthopaedic Research Laboratories, Stanford University, Stanford, CA, United States
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14
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Zhang J, Lei C, Deng Y, Ahmed JZ, Shi D, Lu F. Hypoxia Enhances Mesenchymal Characteristics Maintenance of Buffalo Bone Marrow-Derived Mesenchymal Stem Cells. Cell Reprogram 2020; 22:167-177. [PMID: 32453601 DOI: 10.1089/cell.2019.0097] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Bone marrow-derived mesenchymal stem cells (BMSCs) from livestock are valuable resources for veterinary therapeutics and animal reproduction. Previous studies have shown that hypoxic conditions were beneficial in maintaining the mesenchymal feature of BMSCs. However, the effects of hypoxia on buffalo BMSCs (bBMSCs) remain unclear. In this study, the effects of hypoxic conditions on cell morphology, migration, polarity, and karyotype of bBMSCs were examined. The results showed that hypoxia (5% oxygen) enhanced colony formation and stress fiber synthesis of bBMSCs. Under the hypoxic culture conditions, the migration capacity and normal karyotype rate of bBMSCs were significantly improved (p < 0.05), which resulted in weakened cell polarity and enhanced karyotype stability in bBMSCs. In addition, it was significantly (p < 0.05) upregulated in the expression levels of HIF-TWIST signaling pathway axis-related genes (Hif-1, Hif-2, Twist, Snail, Slug, Fn1, N-cadherin, Collal). The HIF-TWIST axis of bBMSCs was also activated in hypoxia. Finally, it was more effective and easier to maintain the mesenchymal feature of bBMSCs in hypoxic conditions. These findings not only provide theoretical guidance to elucidate the detailed regulation mechanism of hypoxia on mesenchymal nature maintenance of bBMSCs, but also provide positive support to further establish the stable in vitro culture system of bBMSCs.
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Affiliation(s)
- Jun Zhang
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Animal Reproduction Institute, Guangxi University, Nanning, People's Republic of China
| | - Chuan Lei
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Animal Reproduction Institute, Guangxi University, Nanning, People's Republic of China
| | - Yanfei Deng
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Animal Reproduction Institute, Guangxi University, Nanning, People's Republic of China
| | - Jam Zaheer Ahmed
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Animal Reproduction Institute, Guangxi University, Nanning, People's Republic of China
| | - Deshun Shi
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Animal Reproduction Institute, Guangxi University, Nanning, People's Republic of China
| | - Fenghua Lu
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Animal Reproduction Institute, Guangxi University, Nanning, People's Republic of China
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15
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Gabrielyan A, Quade M, Gelinsky M, Rösen-Wolff A. IL-11 and soluble VCAM-1 are important components of Hypoxia Conditioned Media and crucial for Mesenchymal Stromal Cells attraction. Stem Cell Res 2020; 45:101814. [PMID: 32334367 DOI: 10.1016/j.scr.2020.101814] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 04/03/2020] [Accepted: 04/09/2020] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION Bone marrow stromal cells (BMSC) are highly attractive for tissue engineering due to their ability to differentiate into different cell types, to expand extensively in vitro and to release paracrine soluble factors with a high regenerative potential. They were observed to migrate towards the sites of injury in response to chemotactic signals in vivo. During the last years hypoxia has become a proven method to control proliferation, differentiation and multipotency of BMSC. Conditioned medium from hypoxia-treated BMSC (Hypoxia-conditioned Medium; HCM) has been shown to have various favorable properties on tissue regeneration - such as on cell recruitment, wound healing, angiogenesis and revascularization. Due to this regenerative potential many studies attempt to further characterize HCM and its main functional components. In this study we used HCM generated from umbilical cord mesenchymal stem cells (UC-MSC) instead of BMSC, because GMP-verified methods were used to isolate and cultivate the cells and ensure their constant quality. UC-MSC have a high regenerative potential and are still immunologically naive and therefore highly unlikely to cause an immune reaction. In our article we took the first steps to closer investigate the role of umbilical cord MSC-derived HCM components, namely stromal cell-derived factor 1 (SDF-1α), interleukin 11 (IL-11) and soluble vascular cell adhesion molecule 1 (sVCAM-1). RESULTS Our results show previously unknown roles of IL-11 and sVCAM-1 in the attraction of BMSC. The synergistic effect of the investigated protein mixture consisting of IL-11, sVCAM-1 and SDF-1α as well as those recombinant proteins alone revealed a significantly higher chemoattractive capacity towards human BMSC compared to normoxic control medium. Both, the protein mixtures and proteins alone as well as UC-HCM showed an angiogenic effect by promoting the formation of significantly longer tubule structures and higher amounts of junctions and tubules compared to normoxic control medium. CONCLUSIONS By showing the prominent upregulation of IL-11, sVCAM-1 and SDF-1α under hypoxic conditions compared to normoxic control and revealing their crucial role in migration of human BMSC we took a further step forward in characterization of the chemoattractive components of HCM.
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Affiliation(s)
- Anastasia Gabrielyan
- Department of Pediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
| | - Mandy Quade
- Centre for Translational Bone, Joint and Soft Tissue Research, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany
| | - Michael Gelinsky
- Centre for Translational Bone, Joint and Soft Tissue Research, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany
| | - Angela Rösen-Wolff
- Department of Pediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany
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16
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Quade M, Münch P, Lode A, Duin S, Vater C, Gabrielyan A, Rösen‐Wolff A, Gelinsky M. The Secretome of Hypoxia Conditioned hMSC Loaded in a Central Depot Induces Chemotaxis and Angiogenesis in a Biomimetic Mineralized Collagen Bone Replacement Material. Adv Healthc Mater 2020; 9:e1901426. [PMID: 31830380 DOI: 10.1002/adhm.201901426] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Revised: 11/27/2019] [Indexed: 12/18/2022]
Abstract
The development of biomaterials with intrinsic potential to stimulate endogenous tissue regeneration at the site of injury is a main demand on future implants in regenerative medicine. For critical-sized bone defects, an in situ tissue engineering concept is devised based on biomimetic mineralized collagen scaffolds. These scaffolds are functionalized with a central depot loaded with a signaling factor cocktail, obtained from secretome of hypoxia-conditioned human mesenchymal stem cells (MSC). Therefore, hypoxia-conditioned medium (HCM)-production is standardized and adapted to achieve high signaling factor-yields; a concentration protocol based on dialysis and freeze-drying is established to enable the integration of sufficient and defined amounts into the depot. In humid milieu-as after implantation-signaling factors are released by forming a chemotactic gradient, inducing a directed migration of human bone marrow stroma cells (hBMSC) into the scaffold. Angiogenic potential, determined by coculturing human umbilical vein endothelial cells (HUVEC) with osteogenically induced hBMSC shows prevascular structures, which sprout throughout the interconnected pores in a HCM-concentration-dependent manner. Retarded release by alginate-based (1 vol%) depots, significantly improves sprouting-depth and morphology of tubular structures. With the intrinsic potential to supply attracted cells with oxygen and nutrients, this bioactive material system has great potential for clinical translation.
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Affiliation(s)
- Mandy Quade
- Centre for Translational BoneJoint and Soft Tissue ResearchFaculty of Medicine and University Hospital Carl Gustav CarusTechnische Universität Dresden Fetscherstr. 74 01307 Dresden Germany
| | - Pina Münch
- Centre for Translational BoneJoint and Soft Tissue ResearchFaculty of Medicine and University Hospital Carl Gustav CarusTechnische Universität Dresden Fetscherstr. 74 01307 Dresden Germany
| | - Anja Lode
- Centre for Translational BoneJoint and Soft Tissue ResearchFaculty of Medicine and University Hospital Carl Gustav CarusTechnische Universität Dresden Fetscherstr. 74 01307 Dresden Germany
| | - Sarah Duin
- Centre for Translational BoneJoint and Soft Tissue ResearchFaculty of Medicine and University Hospital Carl Gustav CarusTechnische Universität Dresden Fetscherstr. 74 01307 Dresden Germany
| | - Corina Vater
- Centre for Translational BoneJoint and Soft Tissue ResearchFaculty of Medicine and University Hospital Carl Gustav CarusTechnische Universität Dresden Fetscherstr. 74 01307 Dresden Germany
- University Centre of Orthopaedica and TraumatologyFaculty of Medicine and University Hospital Carl Gustav CarusTechnische Universität Dresden Fetscherstr. 74 01307 Dresden Germany
| | - Anastasia Gabrielyan
- Department of PediatricsFaculty of Medicine and University Hospital Carl Gustav CarusTechnische Universität Dresden Fetscherstr. 74 01307 Dresden Germany
| | - Angela Rösen‐Wolff
- Department of PediatricsFaculty of Medicine and University Hospital Carl Gustav CarusTechnische Universität Dresden Fetscherstr. 74 01307 Dresden Germany
| | - Michael Gelinsky
- Centre for Translational BoneJoint and Soft Tissue ResearchFaculty of Medicine and University Hospital Carl Gustav CarusTechnische Universität Dresden Fetscherstr. 74 01307 Dresden Germany
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17
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Loncaric D, Labat V, Debeissat C, Brunet de la Grange P, Rodriguez L, Vlaski-Lafarge M, Ivanovic Z. The majority of cells in so-called "mesenchymal stem cell" population are neither stem cells nor progenitors. Transfus Clin Biol 2018; 26:316-323. [PMID: 30391125 DOI: 10.1016/j.tracli.2018.08.157] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Accepted: 08/18/2018] [Indexed: 01/05/2023]
Abstract
OBJECTIVES The first-passage adherent human bone marrow fibroblast-like cell population corresponds, in terms of phenotype and three-lineage differentiation capacity (assayed in bulk culture), to commonly termed "mesenchymal stem cells". Here we determine the proportion of high proliferative capacity multipotent cells present in this population in order to estimate the proportion of cells that can or cannot be considered as stem and progenitor cells. MATERIAL AND METHODS The single-cell cultures were established starting from human bone marrow-derived first-passage fibroblast-like cells and the proliferating clones were either transferred to secondary cultures to evaluate their further clonogenicity, or split into three wells to assess differentiation into each of the three different lineages. RESULTS The analysis of 197 single-cell cultures from three different bone marrow donors shows that only∼40% of so-called "mesenchymal stem cells" exhibit multipotency and are capable of sustained clonogenicity in secondary cultures. CONCLUSION Even in the first ex vivo passage under favorable conditions the majority (∼60%) of so-called "mesenchymal stem cells" are not multipotent and thus do not represent a stem cell entity.
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Affiliation(s)
- D Loncaric
- Établissement français du sang Nouvelle Aquitaine, scientific department, place Amélie-Raba-Léon, CS21010, 33075 Bordeaux cedex, France; Inserm U1035, université de Bordeaux, 33000 Bordeaux, France
| | - V Labat
- Établissement français du sang Nouvelle Aquitaine, scientific department, place Amélie-Raba-Léon, CS21010, 33075 Bordeaux cedex, France; Inserm U1035, université de Bordeaux, 33000 Bordeaux, France
| | - C Debeissat
- Établissement français du sang Nouvelle Aquitaine, scientific department, place Amélie-Raba-Léon, CS21010, 33075 Bordeaux cedex, France; Inserm U1035, université de Bordeaux, 33000 Bordeaux, France
| | - P Brunet de la Grange
- Établissement français du sang Nouvelle Aquitaine, scientific department, place Amélie-Raba-Léon, CS21010, 33075 Bordeaux cedex, France; Inserm U1035, université de Bordeaux, 33000 Bordeaux, France
| | - L Rodriguez
- Établissement français du sang Nouvelle Aquitaine, scientific department, place Amélie-Raba-Léon, CS21010, 33075 Bordeaux cedex, France; Inserm U1035, université de Bordeaux, 33000 Bordeaux, France
| | - M Vlaski-Lafarge
- Établissement français du sang Nouvelle Aquitaine, scientific department, place Amélie-Raba-Léon, CS21010, 33075 Bordeaux cedex, France; Inserm U1035, université de Bordeaux, 33000 Bordeaux, France
| | - Z Ivanovic
- Établissement français du sang Nouvelle Aquitaine, scientific department, place Amélie-Raba-Léon, CS21010, 33075 Bordeaux cedex, France; Inserm U1035, université de Bordeaux, 33000 Bordeaux, France.
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18
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Studies on Conditioned Media in Human Cells: Evaluation Using Various Cell and Culture Conditions, Animal Disease Models. JOURNAL OF ANIMAL REPRODUCTION AND BIOTECHNOLOGY 2018. [DOI: 10.12750/jet.2018.33.1.41] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
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