A comparison of bone regeneration with human mesenchymal stem cells and muscle-derived stem cells and the critical role of BMP.

A comparison of bone regeneration with human mesenchymal stem cells and muscle-derived stem cells and the critical role of BMP.
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DOI:
10.1016/j.biomaterials.2014.04.113
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发表时间:
2014-08
期刊:
影响因子:
14
通讯作者:
Huard, Johnny
Huard, Johnny
中科院分区:
工程技术1区
文献类型:
--
作者:
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

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成体多能干细胞已经从包括人骨骼肌在内的多种人体组织中分离出来,这代表了一种容易获得的干细胞来源。已经显示,人骨骼肌源性干细胞(hMDSC)是能够多潜能分化的肌肉源性间充质干细胞。虽然hMDSC可以进行成骨分化,并形成骨时,基因修饰表达BMP 2,目前还不清楚是否hMDSC是作为有效的人骨髓间充质干细胞(hBMMSC)的骨再生。目前的研究旨在通过对hMDSC和hBMMSC进行平行比较来评估其成骨和骨再生能力,从而解决这一问题。我们的研究结果表明,hMDSCs和hBMMSCs具有相似的成骨相关基因表达谱,并在体外具有相似的成骨分化能力时,转导表达BMP 2。当使用纤维蛋白密封剂支架时,未转导的hMDSC和hBMMSC在临界尺寸的骨缺损模型中形成非常可忽略的量的骨;然而,当用lenti-BMP 2进行遗传修饰时,两个群体都在缺损区域成功地再生了骨。hMDSC组和hBMMSC组的新骨体积和骨缺损覆盖率无显著差异。虽然两种细胞类型在植入后6周形成成熟的骨组织,但hMDSCs组中新形成的骨比hBMMSCs组经历更快的重塑。总之,我们的研究结果表明,hMDSCs是有效的hBMMSCs在其骨再生能力方面,然而,这两种细胞类型需要与BMP基因修饰,以再生骨在体内。
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 remodeling 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.
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