Cells derived from murine induced pluripotent stem cells (iPSC) by treatment with members of TGF-beta family give rise to osteoblasts differentiation and form bone in vivo.

Cells derived from murine induced pluripotent stem cells (iPSC) by treatment with members of TGF-beta family give rise to osteoblasts differentiation and form bone in vivo.
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DOI:
10.1186/1471-2121-13-35
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发表时间:
2012-12-15
期刊:
影响因子:
--
通讯作者:
Niyibizi C
Niyibizi C
中科院分区:
生物3区
文献类型:
--
作者:
Li F;Niyibizi C

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诱导多能干细胞(iPSC)是利用确定的因子将体细胞重编程为胚胎样状态(ESC)而产生的。由于这些细胞在再生医学中的应用潜力,人们对它们产生了极大的兴趣。将小鼠尾尖成纤维细胞重编程的iPSC单独暴露于维甲酸(RA)或与TGF-β1和3、碱性成纤维细胞生长因子(bFGF)或骨形态发生蛋白2 (BMP-2)联合暴露。由此产生的细胞表达选定的假定的间充质干细胞(MSCs)标记物;体外不同程度向成骨细胞和脂肪细胞分化。tgf - β 1和3衍生的细胞比bFGF或BMP-2衍生的细胞具有更高的分化成成骨细胞的潜力,而BMP-2衍生的细胞表现出更高的向脂肪细胞谱系分化的潜力。TGF-β1联合RA源性细胞植入HA/TCP陶瓷,植入典型骨沉积小鼠。细胞植入支架组织切片的骨特异性蛋白免疫荧光染色证实细胞在体内分化为成骨细胞。结果表明,tgf - β蛋白家族可能被用于生成具有成骨细胞分化和体内骨形成潜力的小鼠iPSC衍生细胞,从而应用于肌肉骨骼组织的修复和再生。
Induced pluripotent stem cells (iPSC) are generated by reprogramming somatic cells into embryonic like state (ESC) using defined factors. There is great interest in these cells because of their potential for application in regenerative medicine. iPSC reprogrammed from murine tail tip fibroblasts were exposed to retinoic acid alone (RA) or in combination with TGF-β1 and 3, basic fibroblast growth factor (bFGF) or bone morphogenetic protein 2 (BMP-2). The resulting cells expressed selected putative mesenchymal stem cells (MSCs) markers; differentiated toward osteoblasts and adipocytic cell lineages in vitro at varying degrees. TGF-beta1 and 3 derived-cells possessed higher potential to give rise to osteoblasts than bFGF or BMP-2 derived-cells while BMP-2 derived cells exhibited a higher potential to differentiate toward adipocytic lineage. TGF-β1 in combination with RA derived-cells seeded onto HA/TCP ceramics and implanted in mice deposited typical bone. Immunofluorescence staining for bone specific proteins in cell seeded scaffolds tissue sections confirmed differentiation of the cells into osteoblasts in vivo. The results demonstrate that TGF-beta family of proteins could potentially be used to generate murine iPSC derived-cells with potential for osteoblasts differentiation and bone formation in vivo and thus for application in musculoskeletal tissue repair and regeneration.
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