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The utilization of decellularized tendon slices to provide an inductive microenvironment for the proliferation and tenogenic differentiation of stem cells
Institution:1. Institute of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China;2. Institute of Stem Cell and Tissue Engineering, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China;1. Department of Orthopaedic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China;2. Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China;3. Lab of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center, Chengdu, Sichuan, P.R. China;1. Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, School of Medicine, Zhejiang University, China;2. Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, China;3. Department of Endocrinology, Shanghai No.5 Hospital, Fudan University, China;4. Department of Orthopaedics, Second Affiliated Hospital, Zhejiang University, China;5. Center for Sport Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, China;6. Faculty of Dentistry, Department of Endodontology, The University of Hong Kong, China;7. Department of Sports Medicine, School of Medicine, Zhejiang University, China;8. China Orthopedic Regenerative Medicine Group (CORMed), China;9. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, China;1. Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, 310058, China;2. Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, 310058, China;3. Department of Sports Medicine, School of Medicine, Zhejiang University, Hangzhou, China;4. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;5. State Key Laboratory for Modi?cation of Chemical Fibers and Polymer Materials, Donghua University, Shanghai, 201620, China;6. College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, China;7. Department of Biosystems Science & Engineering (D-BSSE), ETH-Zurich, Mattenstrasse 26, Basel, 4058, Switzerland;1. Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou 310058, China;2. Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou 310058, China;3. Department of Sports Medicine, School of Medicine, Zhejiang University, Hangzhou 310058, China;4. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China;5. China Orthopedic Regenerative Medicine Group (CORMed), Hangzhou 310058, China;6. College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China;7. Institute of Bionanotechnology and Tissue Engineering, College of Biology, Hunan University, Changsha 410082, China;8. Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China;1. Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea;2. BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
Abstract:The extracellular matrix (ECM) microenvironment for the stem cell niches, including but not limited to the biochemical composition, matrix topography, and stiffness, is crucial to stem cell proliferation and differentiation. The purpose of this study was to explore the capacity of the decellularized tendon slices (DTSs) to induce stem cell proliferation and tenogenic differentiation. Rat adult stem cells, including tendon-derived stem cells (TDSCs) and bone marrow-derived stem cells (BMSCs), were identified to have universal stem cell characteristics. The DTSs were found to retain the native tendon ECM microenvironment cues, including the inherent surface topography, well-preserved tendon ECM biochemical composition and similar stiffness to native tendon. When the TDSCs and BMSCs were cultured on the DTSs respectively, the LIVE/DEAD assay, alamarBlue® assay, scanning electron microscopy examination and qRT-PCR analysis demonstrated that the DTSs have the capacity to support these stem cells homogeneous distribution, alignment, significant proliferation and tenogenic differentiation. Taken together, the findings of this study indicate that the DTSs can provide a naturally inductive microenvironment for the proliferation and tenogenic differentiation of TDSCs and BMSCs, supporting the use of decellularized tendon ECM as a promising and valuable approach for tendon repair/reconstruction.
Keywords:Decellularized tendon slices  Tendon-derived stem cells  Bone marrow-derived stem cells  Microenvironment  Proliferation  Differentiation
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