Journal article
BMP2 Is Superior to BMP4 for Promoting Human Muscle-Derived Stem Cell-Mediated Bone Regeneration in a Critical-Sized Calvarial Defect Model
Cell transplantation, Vol.22(12), pp.2393-2408
11/01/2012
DOI: 10.3727/096368912X658854
PMCID: PMC4361002
PMID: 23244588
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.
Details
- Title: Subtitle
- BMP2 Is Superior to BMP4 for Promoting Human Muscle-Derived Stem Cell-Mediated Bone Regeneration in a Critical-Sized Calvarial Defect Model
- Creators
- Xueqin Gao - Stem Cell Research Center, Growth and Developmental Laboratory, Department of Orthopaedic Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA Molecular Therapy Laboratory, Department of Orthopaedic Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USAArvydas Usas - University of PittsburghAiping Lu - University of PittsburghYing Tang - University of PittsburghBing Wang - University of PittsburghChien-Wen Chen - University of PittsburghHongshuai Li - University of PittsburghJessica C. Tebbets - University of PittsburghJames H. Cummins - University of PittsburghJohnny Huard - University of Pittsburgh
- Resource Type
- Journal article
- Publication Details
- Cell transplantation, Vol.22(12), pp.2393-2408
- DOI
- 10.3727/096368912X658854
- PMID
- 23244588
- PMCID
- PMC4361002
- NLM abbreviation
- Cell Transplant
- ISSN
- 0963-6897
- eISSN
- 1555-3892
- Language
- English
- Date published
- 11/01/2012
- Academic Unit
- Orthopedics and Rehabilitation; Radiation Oncology
- Record Identifier
- 9984303978802771
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