Chondrocytes, Mesenchymal Stem Cells, and Their Combination in Articular Cartilage Regenerative Medicine

Ann Biomed Eng. 2016 May;44(5):1325-54. doi: 10.1007/s10439-016-1575-9. Epub 2016 Mar 17.


Articular cartilage (AC) is a highly organized connective tissue lining, covering the ends of bones within articulating joints. Its highly ordered structure is essential for stable motion and provides a frictionless surface easing load transfer. AC is vulnerable to lesions and, because it is aneural and avascular, it has limited self-repair potential which often leads to osteoarthritis. To date, no fully successful treatment for osteoarthritis has been reported. Thus, the development of innovative therapeutic approaches is desperately needed. Autologous chondrocyte implantation, the only cell-based surgical intervention approved in the United States for treating cartilage defects, has limitations because of de-differentiation of articular chondrocytes (AChs) upon in vitro expansion. De-differentiation can be abated if initial populations of AChs are co-cultured with mesenchymal stem cells (MSCs), which not only undergo chondrogenesis themselves but also support chondrocyte vitality. In this review we summarize studies utilizing AChs, non-AChs, and MSCs and compare associated outcomes. Moreover, a comprehensive set of recent human studies using chondrocytes to direct MSC differentiation, MSCs to support chondrocyte re-differentiation and proliferation in co-culture environments, and exploratory animal intra- and inter-species studies are systematically reviewed and discussed in an innovative manner allowing side-by-side comparisons of protocols and outcomes. Finally, a comprehensive set of recommendations are made for future studies.

Keywords: Articular cartilage; Articular cartilage tissue engineering; Autologous chondrocyte implantation; Autologous mesenchymal stem cell transplantation; Chondrocytes; Co-culture of mesenchymal stem cells with articular chondrocytes; Mesenchymal stem cells.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Autografts
  • Cartilage, Articular / metabolism*
  • Cell Culture Techniques / methods
  • Cell Dedifferentiation
  • Cell Proliferation
  • Chondrocytes / cytology
  • Chondrocytes / metabolism
  • Chondrocytes / transplantation*
  • Humans
  • Joint Diseases / metabolism
  • Joint Diseases / therapy*
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Regenerative Medicine / methods*