Generation of iPSC-derived limb progenitor-like cells for stimulating phalange regeneration in the adult mouse.

Generation of iPSC-derived limb progenitor-like cells for stimulating phalange regeneration in the adult mouse.
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生成 iPSC 衍生的肢体祖细胞样细胞,用于刺激成年小鼠指骨再生

DOI:
10.1038/celldisc.2017.46
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发表时间:
2017
期刊:
影响因子:
33.5
通讯作者:
Lin G
Lin G
中科院分区:
生物学1区
文献类型:
--
作者:
Chen Y;Xu H;Lin G

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在啮齿动物和人类中观察到的指尖再生能力为促进哺乳动物的稳健再生奠定了基础。然而,刺激更近端水平的再生,例如成年小鼠的中指骨(P2),仍然具有挑战性。在证明肢体祖细胞移植在刺激非洲爪蟾肢体再生方面的有效性后,我们现在将细胞移植方法应用于成年小鼠。在这里,我们报道胚胎和诱导多能干细胞 (iPSC) 衍生的肢体祖细胞样细胞都可以促进成年小鼠 P2 再生。我们建立了一种简单有效的方案,用于从小鼠 iPSC 中衍生出肢体祖细胞样细胞。 iPSC 以三维纤维蛋白体的形式培养,然后在分化过程中使用 Fgf8、CHIR99021、Purmorphamine 和 SB43542 组合进行处理。这些 iPSC 衍生的肢体祖细胞在肢体相关基因的表达方面类似于胚胎肢体间充质细胞。移植后,肢体祖细胞样细胞可以像胚胎肢芽细胞一样促进成年小鼠P2再生。我们的结果为进一步开发基于祖细胞的方法来改善成年小鼠四肢的再生提供了基础。
The capacity of digit tip regeneration observed both in rodents and humans establishes a foundation for promoting robust regeneration in mammals. However, stimulating regeneration at more proximal levels, such as the middle phalanges (P2) of the adult mouse, remains challenging. Having shown the effectiveness of transplantation of limb progenitor cells in stimulating limb regeneration in Xenopus, we are now applying the cell transplantation approach to the adult mouse. Here we report that both embryonic and induced pluripotent stem cell (iPSC)-derived limb progenitor-like cells can promote adult mouse P2 regeneration. We have established a simple and efficient protocol for deriving limb progenitor-like cells from mouse iPSCs. iPSCs are cultured as three-dimensional fibrin bodies, followed by treatment with combinations of Fgf8, CHIR99021, Purmorphamine and SB43542 during differentiation. These iPSC-derived limb progenitor-like cells resemble embryonic limb mesenchyme cells in their expression of limb-related genes. After transplantation, the limb progenitor-like cells can promote adult mouse P2 regeneration, as embryonic limb bud cells do. Our results provide a basis for further developing progenitor cell-based approaches for improving regeneration in the adult mouse limbs.
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