Gao Xueqin, Usas Arvydas, Tang Ying, Lu Aiping, Tan Jian, Schneppendahl Johannes, Kozemchak Adam M, Wang Bing, Cummins James H, Tuan Rocky S, Huard Johnny
Stem Cell Research Center, University of Pittsburgh, Pittsburgh, PA, United States.
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.
Biomaterials. 2014 Aug;35(25):6859-70. doi: 10.1016/j.biomaterials.2014.04.113. Epub 2014 May 21.
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.
成人多能干细胞已从包括人类骨骼肌在内的多种人体组织中分离出来,骨骼肌是一种易于获取的干细胞来源。研究表明,人类骨骼肌来源的干细胞(hMDSCs)是能够进行多能分化的肌肉来源间充质干细胞。尽管hMDSCs在经过基因改造以表达BMP2时可发生成骨分化并形成骨组织,但hMDSCs在骨再生方面是否与人类骨髓间充质干细胞(hBMMSCs)一样高效仍不清楚。当前研究旨在通过对hMDSCs和hBMMSCs进行平行比较来评估它们的成骨和骨再生能力,从而解决这一问题。我们的结果表明,hMDSCs和hBMMSCs具有相似的成骨相关基因表达谱,在转导以表达BMP2时,它们在体外具有相似的成骨分化能力。在使用纤维蛋白密封剂支架的临界尺寸骨缺损模型中,未转导的hMDSCs和hBMMSCs形成的骨量都极少;然而,当用慢病毒载体-BMP2进行基因改造时,这两种细胞群体都能在缺损区域成功再生骨组织。hMDSC组和hBMMSC组在新形成的骨体积和骨缺损覆盖率方面没有发现显著差异。尽管两种细胞类型在植入后6周都形成了成熟的骨组织,但hMDSCs组新形成的骨组织比hBMMSCs组经历了更快的重塑过程。总之,我们的结果表明,hMDSCs在骨再生能力方面与hBMMSCs一样高效;然而,为了在体内再生骨组织,这两种细胞类型都需要用BMP进行基因改造。