Open AccessAnalysis of Bone‐Cartilage‐Stromal Progenitor Populations in Trauma Induced and Genetic Models of Heterotopic Ossification
Author(s) -
Agarwal Shailesh,
Loder Shawn J.,
Sorkin Michael,
Li Shuli,
Shrestha Swati,
Zhao Bin,
Mishina Yuji,
James Aaron W.,
Levi Benjamin
Publication year - 2016
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2376
Subject(s) - biology , heterotopic ossification , bone morphogenetic protein , transplantation , progenitor cell , cartilage , ossification , stromal cell , endochondral ossification , chondrogenesis , anatomy , pathology , microbiology and biotechnology , stem cell , cancer research , medicine , genetics , gene
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/caAcvr1 fl/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. S tem C ells 2016;34:1692–1701