title: A comparison of bone regeneration with human mesenchymal stem cells and muscle-derived stem cells and the critical role of BMP.
abstract: Adult multipotent stem cells have been isolated from a variety of human tissues including human skeletal muscle, which represent an easily accessible source of stem cells. It has been shown that human skeletal muscle-derived stem cells (hMDSCs) are muscle-derived mesenchymal stem cells capable of multipotent differentiation. Although hMDSCs can undergo osteogenic differentiation and form bone when genetically modified to express BMP2; it is still unclear whether hMDSCs are as efficient as human bone marrow mesenchymal stem cells (hBMMSCs) for bone regeneration. The current study aimed to address this question by performing a parallel comparison between hMDSCs and hBMMSCs to evaluate their osteogenic and bone regeneration capacities. Our results demonstrated that hMDSCs and hBMMSCs had similar osteogenic-related gene expression profiles and had similar osteogenic differentiation capacities in vitro when transduced to express BMP2. Both the untransduced hMDSCs and hBMMSCs formed very negligible amounts of bone in the critical sized bone defect model when using a fibrin sealant scaffold; however, when genetically modified with lenti-BMP2, both populations successfully regenerated bone in the defect area. No significant differences were found in the newly formed bone volumes and bone defect coverage between the hMDSC and hBMMSC groups. Although both cell types formed mature bone tissue by 6 weeks post-implantation, the newly formed bone in the hMDSCs group underwent quicker remodelling than the hBMMSCs group. In conclusion, our results demonstrated that hMDSCs are as efficient as hBMMSCs in terms of their bone regeneration capacity; however, both cell types required genetic modification with BMP in order to regenerate bone in vivo.
authors.affiliation: Stem Cell Research Center, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Gao
authors.affiliation: Stem Cell Research Center, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Arvydas
authors.initials: A
authors.lastname: Usas
authors.affiliation: Stem Cell Research Center, University of Pittsburgh, Pittsburgh, PA, United States; Molecular Therapy Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Stem Cell Research Center, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Aiping
authors.initials: A
authors.lastname: Lu
authors.affiliation: Center for Cellular and Molecular Engineering, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Jian
authors.initials: J
authors.lastname: Tan
authors.affiliation: Stem Cell Research Center, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schneppendahl
authors.affiliation: Neuroscience Program, University of Michigan Class of 2013, Pittsburgh Tissue Engineering Initiative Summer Internship, United States.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Kozemchak
authors.affiliation: Molecular Therapy Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: Stem Cell Research Center, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: James H
authors.initials: JH
authors.lastname: Cummins
authors.affiliation: Center for Cellular and Molecular Engineering, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Rocky S
authors.initials: RS
authors.lastname: Tuan
authors.affiliation: Stem Cell Research Center, University of Pittsburgh, Pittsburgh, PA, United States. Electronic address: jhuard@pitt.edu.
authors.forename: Johnny
authors.initials: J
authors.lastname: Huard
mesh_terms: D000328:Adult; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism; D001861:Bone Regeneration / Q000502:physiology*; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D039902:Multipotent Stem Cells / Q000378:metabolism; D032342:Muscle Cells / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology; D023822:Tissue Engineering; D059467:Transcriptome; D014161:Transduction, Genetic; D055815:Young Adult
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2
keywords: BMP2; Bone tissue engineering; Calvarial defect; Human bone marrow mesenchymal stem cells; Human muscle-derived stem cells; Lentivirus