@article{8b7eb1bece8841baaff1b12d71f29440,
title = "Analysis of Bone-Cartilage-Stromal Progenitor Populations in Trauma Induced and Genetic Models of Heterotopic Ossification",
abstract = "Heterotopic ossification (HO), the formation of extra-skeletal bone in soft tissues, is a pathologic process occurring after substantial burns or trauma, or in patients with type I bone morphogenetic protein (BMP) receptor hyperactivating mutations. Identifying the cells responsible for de novo bone formation during adulthood is of critical importance for therapeutic and regenerative purposes. Using a model of trauma-induced HO with hind limb Achilles' tenotomy and dorsal burn injury and a genetic nontrauma HO model (Nfatc1-Cre/caAcvr1fl/wt), we demonstrate enrichment of previously defined bone-cartilage-stromal progenitor cells (BCSP: AlphaV+/CD105+/Tie2-/CD45-/Thy1-/6C3-) at the site of HO formation when compared with marrow isolated from the ipsilateral hind limb, or from tissue of the contralateral, uninjured hind limb. Upon transplantation into tenotomy sites soon after injury, BCSPs isolated from neonatal mice or developing HO incorporate into the developing lesion in cartilage and bone and express chondrogenic and osteogenic transcription factors. Additionally, BCSPs isolated from developing HO similarly incorporate into new HO lesions upon transplantation. Finally, adventitial cells, but not pericytes, appear to play a supportive role in HO formation. Our findings indicate that BCSPs contribute to de novo bone formation during adulthood and may hold substantial regenerative potential.",
keywords = "Bone, Bone marrow stromal cells, Cell migration, Chondrogenesis, Experimental models, Pericytes, Progenitor cells",
author = "Shailesh Agarwal and Loder, {Shawn J.} and Michael Sorkin and Shuli Li and Swati Shrestha and Bin Zhao and Yuji Mishina and James, {Aaron W.} and Benjamin Levi",
note = "Funding Information: S.A. was supported by the Coller Society Research Fellowship, NIH Loan Repayment Program, NIH, F32AR06649901A1, and Plastic Surgery Foundation. S.J.L. was supported by the Howard Hughes Medical Institute (HHMI) Medical Fellows Program. Y.M. was supported by NIH R01DE020843. B.L. was supported by funding from NIH/National Institute of General Medical Sciences Grant K08GM109105-0, Plastic Surgery Foundation National Endowment Award, the Association for Academic Surgery Roslyn Award, American Association for the Surgery of Trauma Research & Education Foundation Scholarship, DOD: W81XWH-14-DMRDP-CRMRP-NMSIRA and American Association of Plastic Surgery Research Fellowship. This work was partially supported by DOD work units W81XWH-14-2-0010 and 602115HP.3720.001.A1014. Some of the authors are employees of the United States Government. This work was prepared as part of their official duties. Title 17 U.S.C. §105 provides that “Copyright protection under this title is not available for any work of the United States Government.” Title 17 U.S.C §101 defined a US Government work as a work prepared by a military service member or employees of the United States Government as part of that person{\textquoteright}s official duties. The opinions or assertions contained in this paper are the private views of the authors and are not to be construed as reflecting the views, policy or positions of the Department of the Navy, Department of Defense nor the United States Government. Funding Information: A.W.J was supported by the UCLA Daljit S. and Elaine Sarka-ria Fellowship award, the Orthopaedic Research and Education Foundation with funding provided by the Musculoskeletal Transplant Foundation, and NIH/NIAMS K08 AR068316-01 Publisher Copyright: {\textcopyright} 2016 AlphaMed Press.",
year = "2016",
month = jun,
day = "1",
doi = "10.1002/stem.2376",
language = "English",
volume = "34",
pages = "1692--1701",
journal = "Stem Cells",
issn = "1066-5099",
number = "6",
}