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Analysis of Bone-Cartilage-Stromal Progenitor Populations in Trauma Induced and Genetic Models of Heterotopic Ossification.
Stem Cells. 2016 06; 34(6):1692-701.SC

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/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. Stem Cells 2016;34:1692-1701.

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Publisher Full Text
ncbi.nlm.nih.gov
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Authors+Show Affiliations

Agarwal S
Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Loder SJ
Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Sorkin M
Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Li S
Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Shrestha S
Department of Pathology & Laboratory Medicine and Orthopaedic Hospital Research Center, University of California, Los Angeles.
Zhao B
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
Mishina Y
School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA.
James AW
Department of Pathology & Laboratory Medicine and Orthopaedic Hospital Research Center, University of California, Los Angeles.
Levi B
Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.

MeSH

Achilles TendonAnimalsAnimals, NewbornBone and BonesCartilageDisease Models, AnimalHumansMaleMice, Inbred C57BLModels, GeneticOssification, HeterotopicOsteoblastsOsteogenesisPericytesStem Cell TransplantationStem CellsStromal CellsTenotomyWounds and Injuries

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27068890

Citation

Agarwal, Shailesh, et al. "Analysis of Bone-Cartilage-Stromal Progenitor Populations in Trauma Induced and Genetic Models of Heterotopic Ossification." Stem Cells (Dayton, Ohio), vol. 34, no. 6, 2016, pp. 1692-701.
Agarwal S, Loder SJ, Sorkin M, et al. Analysis of Bone-Cartilage-Stromal Progenitor Populations in Trauma Induced and Genetic Models of Heterotopic Ossification. Stem Cells. 2016;34(6):1692-701.
Agarwal, S., Loder, S. J., Sorkin, M., Li, S., Shrestha, S., Zhao, B., Mishina, Y., James, A. W., & Levi, B. (2016). Analysis of Bone-Cartilage-Stromal Progenitor Populations in Trauma Induced and Genetic Models of Heterotopic Ossification. Stem Cells (Dayton, Ohio), 34(6), 1692-701. https://doi.org/10.1002/stem.2376
Agarwal S, et al. Analysis of Bone-Cartilage-Stromal Progenitor Populations in Trauma Induced and Genetic Models of Heterotopic Ossification. Stem Cells. 2016;34(6):1692-701. PubMed PMID: 27068890.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of Bone-Cartilage-Stromal Progenitor Populations in Trauma Induced and Genetic Models of Heterotopic Ossification. AU - Agarwal,Shailesh, AU - Loder,Shawn J, AU - Sorkin,Michael, AU - Li,Shuli, AU - Shrestha,Swati, AU - Zhao,Bin, AU - Mishina,Yuji, AU - James,Aaron W, AU - Levi,Benjamin, Y1 - 2016/05/18/ PY - 2015/07/14/received PY - 2016/03/14/accepted PY - 2016/4/13/entrez PY - 2016/4/14/pubmed PY - 2017/12/5/medline KW - Bone KW - Bone marrow stromal cells KW - Cell migration KW - Chondrogenesis KW - Experimental models KW - Pericytes KW - Progenitor cells SP - 1692 EP - 701 JF - Stem cells (Dayton, Ohio) JO - Stem Cells VL - 34 IS - 6 N2 - 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. Stem Cells 2016;34:1692-1701. SN - 1549-4918 UR - https://www.unboundmedicine.com/medline/citation/27068890/Analysis_of_Bone_Cartilage_Stromal_Progenitor_Populations_in_Trauma_Induced_and_Genetic_Models_of_Heterotopic_Ossification_ L2 - https://doi.org/10.1002/stem.2376 DB - PRIME DP - Unbound Medicine ER -