Articular cartilage regeneration by activated skeletal stem cells

Matthew P. Murphy, Lauren S. Koepke, Michael T. Lopez, Xinming Tong, Thomas H. Ambrosi, Gunsagar S. Gulati, Owen Marecic, Yuting Wang, Ryan C. Ransom, Malachia Y. Hoover, Holly Steininger, Liming Zhao, Marcin P. Walkiewicz, Natalina Quarto, Benjamin Levi, Derrick C. Wan, Irving L. Weissman, Stuart B. Goodman, Fan Yang, Michael T. Longaker*Charles K.F. Chan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

188 Scopus citations


Osteoarthritis (OA) is a degenerative disease resulting in irreversible, progressive destruction of articular cartilage1. The etiology of OA is complex and involves a variety of factors, including genetic predisposition, acute injury and chronic inflammation2–4. Here we investigate the ability of resident skeletal stem-cell (SSC) populations to regenerate cartilage in relation to age, a possible contributor to the development of osteoarthritis5–7. We demonstrate that aging is associated with progressive loss of SSCs and diminished chondrogenesis in the joints of both mice and humans. However, a local expansion of SSCs could still be triggered in the chondral surface of adult limb joints in mice by stimulating a regenerative response using microfracture (MF) surgery. Although MF-activated SSCs tended to form fibrous tissues, localized co-delivery of BMP2 and soluble VEGFR1 (sVEGFR1), a VEGF receptor antagonist, in a hydrogel skewed differentiation of MF-activated SSCs toward articular cartilage. These data indicate that following MF, a resident stem-cell population can be induced to generate cartilage for treatment of localized chondral disease in OA.

Original languageEnglish
Pages (from-to)1583-1592
Number of pages10
JournalNature Medicine
Issue number10
StatePublished - 1 Oct 2020
Externally publishedYes


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