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Can one generate stable hyaline cartilage from adult mesenchymal stem cells? A developmental approach
Author(s) -
Hellingman Catharine A.,
Koevoet Wendy,
Osch Gerjo J. V. M.
Publication year - 2012
Publication title -
journal of tissue engineering and regenerative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.835
H-Index - 72
eISSN - 1932-7005
pISSN - 1932-6254
DOI - 10.1002/term.502
Subject(s) - chondrogenesis , mesenchymal stem cell , hyaline cartilage , cartilage , microbiology and biotechnology , stem cell , embryonic stem cell , stem cell transplantation for articular cartilage repair , chondrocyte , chemistry , cellular differentiation , pathology , biology , anatomy , adult stem cell , medicine , osteoarthritis , biochemistry , articular cartilage , alternative medicine , gene
Chondrogenically differentiating bone marrow‐derived mesenchymal stem cells (BMSCs) display signs of chondrocyte hypertrophy, such as production of collagen type X, MMP13 and alkaline phosphatase (ALPL). For cartilage reconstructions this is undesirable, as terminally differentiated cartilage produced by BMSCs mineralizes when implanted in vivo . Terminal differentiation is not restricted to BMSCs but is also encountered in chondrogenic differentiation of adipose‐derived mesenchymal stem cells (MSCs) as well as embryonic stem cells, which by definition should be able to generate all types of tissues, including stable cartilage. Therefore, we propose that the currently used culture conditions may drive the cells towards terminal differentiation. In this manuscript we aim to review the literature, supplemented by our own data to answer the question, is it possible to generate stable hyaline cartilage from adult MSCs? We demonstrate that recently published methods for inhibiting terminal differentiation (through PTHrP, MMP13 or blocking phosphorylation of Smad1/5/8) result in cartilage formation with reduction of hypertrophic markers, although this does not reach the low level of stable chondrocytes. A set of hypertrophy markers should be included in future studies to characterize the phenotype more precisely. Finally, we used what is currently known in developmental biology about the differential development of hyaline and terminally differentiated cartilage to provide thought and insights to change current culture models for creating hyaline cartilage. Inhibiting terminal differentiation may not result in stable hyaline cartilage if the right balance of signals has not been created from the start of culture onwards. Copyright © 2011 John Wiley & Sons, Ltd.