Exploiting endogenous fibrocartilage stem cells to regenerate cartilage and repair joint injury

Mildred C. Embree (), Mo Chen, Serhiy Pylawka, Danielle Kong, George M. Iwaoka, Ivo Kalajzic, Hai Yao, Chancheng Shi, Dongming Sun, Tzong-Jen Sheu, David A. Koslovsky, Alia Koch and Jeremy J. Mao
Additional contact information
Mildred C. Embree: TMJ Biology and Regenerative Medicine Laboratory, College of Dental Medicine, Columbia University Medical Center
Mo Chen: Center for Craniofacial Regeneration, College of Dental Medicine, Columbia University Medical Center
Serhiy Pylawka: TMJ Biology and Regenerative Medicine Laboratory, College of Dental Medicine, Columbia University Medical Center
Danielle Kong: Center for Craniofacial Regeneration, College of Dental Medicine, Columbia University Medical Center
George M. Iwaoka: Center for Craniofacial Regeneration, College of Dental Medicine, Columbia University Medical Center
Ivo Kalajzic: MC3705, L7005, University of Connecticut Health Sciences Center
Hai Yao: Clemson-MUSC Bioengineering Program, Clemson University
Chancheng Shi: Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences
Dongming Sun: W.M. Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey
Tzong-Jen Sheu: Center for Musculoskeletal Research, University of Rochester Medical Center
David A. Koslovsky: Metropolitan Oral Surgery Associates, 488 Madison Avenue, #200
Alia Koch: College of Dental Medicine, Columbia University Medical Center
Jeremy J. Mao: Center for Craniofacial Regeneration, College of Dental Medicine, Columbia University Medical Center

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract Tissue regeneration using stem cell-based transplantation faces many hurdles. Alternatively, therapeutically exploiting endogenous stem cells to regenerate injured or diseased tissue may circumvent these challenges. Here we show resident fibrocartilage stem cells (FCSCs) can be used to regenerate and repair cartilage. We identify FCSCs residing within the superficial zone niche in the temporomandibular joint (TMJ) condyle. A single FCSC spontaneously generates a cartilage anlage, remodels into bone and organizes a haematopoietic microenvironment. Wnt signals deplete the reservoir of FCSCs and cause cartilage degeneration. We also show that intra-articular treatment with the Wnt inhibitor sclerostin sustains the FCSC pool and regenerates cartilage in a TMJ injury model. We demonstrate the promise of exploiting resident FCSCs as a regenerative therapeutic strategy to substitute cell transplantation that could be beneficial for patients suffering from fibrocartilage injury and disease. These data prompt the examination of utilizing this strategy for other musculoskeletal tissues.

Date: 2016
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DOI: 10.1038/ncomms13073

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