@article{5600546fa1374d9cad15638bc0d8092c,
title = "Articular cartilage regeneration by activated skeletal stem cells",
abstract = "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.",
author = "Murphy, {Matthew P.} and Koepke, {Lauren S.} and Lopez, {Michael T.} and Xinming Tong and Ambrosi, {Thomas H.} and Gulati, {Gunsagar S.} and Owen Marecic and Yuting Wang and Ransom, {Ryan C.} and Hoover, {Malachia Y.} and Holly Steininger and Liming Zhao and Walkiewicz, {Marcin P.} and Natalina Quarto and Benjamin Levi and Wan, {Derrick C.} and Weissman, {Irving L.} and Goodman, {Stuart B.} and Fan Yang and Longaker, {Michael T.} and Chan, {Charles K.F.}",
note = "Funding Information: The authors thank N. Williams, C. Queen, C. Crumpton, E. Kang, M. Butcher, L. Quinn, P. Perira and R. Mann for advice and assistance, and A. McCarty, M. Alvarez, and VSC Staff for animal model support. The authors also thank M. Ekhart, and the PAN facility at Stanford for help in gene-expression analysis. In addition, the authors thank S. Goodman and the Orthopedic Department of Stanford for donation of human adult specimens. The study was supported by NIH (R01 DE027323, R56 DE025597, R01 DE026730, R01 DE021683, R21 DE024230, U01HL099776, U24DE026914 and R21 DE019274), CIRMTR1-01249, Oak Foundation, Hagey Laboratory, Pitch Johnson Fund and Gunn/Olivier Research Fund to M.T. Longaker; Siebel Fellowship, PCF YI Award, Stinehart/Reed, and NIHNIAK99AG049958-01A1, American Federation of Aging Research and Arthritis National Research Foundation to C.K.F.C.; HHMI Fellowship to G.S.G.; the German Research Foundation (DFG) Fellowship 399915929 to T.H.A.; NIH, NIGMS R01GM123069, NIH1R01AR071379, ACS Clowes Award, Department of Defense CDMRP W81XWH-18-1-0653, OR170174 to B.L; PSRF National Endowment and Stanford TTE fellowship to M.P.M.; NIHS10 RR02933801 to Stanford Stem Cell FACS core. The project was supported, in part, by Award Number 1S10OD021514-01 from the National Center for Research Resources (NCRR). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCRR or the National Institutes of Health. Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2020",
month = oct,
day = "1",
doi = "10.1038/s41591-020-1013-2",
language = "English",
volume = "26",
pages = "1583--1592",
journal = "Nature Medicine",
issn = "1078-8956",
number = "10",
}