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BMP2 Is superior to BMP4 for promoting human muscle-derived stem cell-mediated bone regeneration in a critical-sized calvarial defect model

Gao, X and Usas, A and Lu, A and Tang, Y and Wang, B and Chen, CW and Li, H and Tebbets, JC and Cummins, JH and Huard, J (2013) BMP2 Is superior to BMP4 for promoting human muscle-derived stem cell-mediated bone regeneration in a critical-sized calvarial defect model. Cell Transplantation, 22 (12). 2393 - 2408. ISSN 0963-6897

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Abstract

Muscle-derived cells have been successfully isolated using a variety of different methods and have been shown to possess multilineage differentiation capacities, including an ability to differentiate into articular cartilage and bone in vivo; however, the characterization of human muscle-derived stem cells (hMDSCs) and their bone regenerative capacities have not been fully investigated. Genetic modification of these cells may enhance their osteogenic capacity, which could potentially be applied to bone regenerative therapies. We found that hMDSCs, isolated by the preplate technique, consistently expressed the myogenic marker CD56, the pericyte/endothelial cell marker CD146, and the mesenchymal stem cell markers CD73, CD90, CD105, and CD44 but did not express the hematopoietic stem cell marker CD45, and they could undergo osteogenic, chondrogenic, adipogenic, and myogenic differentiation in vitro. In order to investigate the osteoinductive potential of hMDSCs, we constructed a retroviral vector expressing BMP4 and GFP and a lentiviral vector expressing BMP2. The BMP4-expressing hMDSCs were able to undergo osteogenic differentiation in vitro and exhibited enhanced mineralization compared to nontransduced cells; however, when transplanted into a calvarial defect, they failed to regenerate bone. Local administration of BMP4 protein and cell pretreatment with N-acetylcysteine (NAC), which improves cell survival, did not enhance the osteogenic capacity of the retro-BMP4-transduced cells. In contrast, lenti-BMP2-transduced hMDSCs not only exhibited enhanced in vitro osteogenic differentiation but also induced robust bone formation and nearly completely healed a critical-sized calvarial defect in CD-1 nude mice 6 weeks following transplantation. Herovici's staining of the regenerated bone demonstrated that the bone matrix contained a large amount of type I collagen. Our findings indicated that the hMDSCs are likely mesenchymal stem cells of muscle origin and that BMP2 is more efficient than BMP4 in promoting the bone regenerative capacity of the hMDSCs in vivo. © 2013 Cognizant Comm. Corp.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Gao, X
Usas, A
Lu, A
Tang, Yyit3@pitt.eduYIT3
Wang, Bbingwang@pitt.eduBINGWANG
Chen, CW
Li, HHongshuai.li@pitt.eduHOL24
Tebbets, JCjct13@pitt.eduJCT13
Cummins, JH
Huard, J
Centers: Other Centers, Institutes, or Units > Stem Cell Research Center
Date: 19 December 2013
Date Type: Publication
Journal or Publication Title: Cell Transplantation
Volume: 22
Number: 12
Page Range: 2393 - 2408
DOI or Unique Handle: 10.3727/096368912x658854
Schools and Programs: School of Medicine > Orthopaedic Surgery
Refereed: Yes
ISSN: 0963-6897
PubMed ID: 23244588
Date Deposited: 04 Apr 2014 15:58
Last Modified: 02 Feb 2019 16:56
URI: http://d-scholarship.pitt.edu/id/eprint/20885

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