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Proc Natl Acad Sci U S A. 2014 May 13;111(19):6940-5. doi: 10.1073/pnas.1324050111. Epub 2014 Apr 28.

Large, stratified, and mechanically functional human cartilage grown in vitro by mesenchymal condensation.

Author information

1
Department of Biomedical Engineering, Columbia University, New York, NY 10032;
2
Department of Mechanical Engineering, Columbia University, New York, NY 10027; and.
3
Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180.
4
Department of Biomedical Engineering, Columbia University, New York, NY 10032; gv2131@columbia.edu.

Abstract

The efforts to grow mechanically functional cartilage from human mesenchymal stem cells have not been successful. We report that clinically sized pieces of human cartilage with physiologic stratification and biomechanics can be grown in vitro by recapitulating some aspects of the developmental process of mesenchymal condensation. By exposure to transforming growth factor-β, mesenchymal stem cells were induced to condense into cellular bodies, undergo chondrogenic differentiation, and form cartilagenous tissue, in a process designed to mimic mesenchymal condensation leading into chondrogenesis. We discovered that the condensed mesenchymal cell bodies (CMBs) formed in vitro set an outer boundary after 5 d of culture, as indicated by the expression of mesenchymal condensation genes and deposition of tenascin. Before setting of boundaries, the CMBs could be fused into homogenous cellular aggregates giving rise to well-differentiated and mechanically functional cartilage. We used the mesenchymal condensation and fusion of CMBs to grow centimeter-sized, anatomically shaped pieces of human articular cartilage over 5 wk of culture. For the first time to our knowledge biomechanical properties of cartilage derived from human mesenchymal cells were comparable to native cartilage, with the Young's modulus of >800 kPa and equilibrium friction coeffcient of <0.3. We also demonstrate that CMBs have capability to form mechanically strong cartilage-cartilage interface in an in vitro cartilage defect model. The CMBs, which acted as "lego-like" blocks of neocartilage, were capable of assembling into human cartilage with physiologic-like structure and mechanical properties.

KEYWORDS:

biomimetic; cartilage mechanics; cartilage repair; regenerative medicine; tissue engineering

PMID:
24778247
PMCID:
PMC4024923
DOI:
10.1073/pnas.1324050111
[Indexed for MEDLINE]
Free PMC Article

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