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Differentiation and Molecular Properties of Mesenchymal Stem Cells Derived from Murine Induced Pluripotent Stem Cells Derived on Gelatin or Collagen

机译:明胶或胶原衍生的鼠诱导多能干细胞衍生的间充质干细胞的分化和分子特性

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摘要

The generation of induced-pluripotential stem cells- (iPSCs-) derived mesenchymal stem cells (iMSCs) is an attractive and promising approach for preparing large, uniform batches of applicable MSCs that can serve as an alternative cell source of primary MSCs. Appropriate culture surfaces may influence their growth and differentiation potentials during iMSC derivation. The present study compared molecular properties and differentiation potential of derived mouse iPS-MSCs by deriving on gelatin or collagen-coated surfaces. The cells were derived by a one-step method and expressed CD73 and CD90, but CD105 was downregulated in iMSCs cultured only on gelatin-coated plates with increasing numbers of passages. A pairwise scatter analysis revealed similar expression of MSC-specific genes in iMSCs derived on gelatin and on collagen surfaces as well as in primary mouse bone marrow MSCs. Deriving iMSCs on gelatin and collagen dictated their osteogenic and adipose differentiation potentials, respectively. Derived iMSCs on gelatin upregulated Bmp2 and Lif prior to induction of osteogenic or adipose differentiation, while PPARγ was upregulated by deriving on collagen. Our results suggest that extracellular matrix components such as gelatin biases generated iMSC differentiation potential towards adipose or bone tissue in their derivation process via up- or downregulation of these master genes.
机译:诱导多能干细胞(iPSCs)衍生的间充质干细胞(iMSCs)的产生是一种诱人且有前途的方法,可用于制备大批量,均匀批次的适用MSC,这些MSC可以用作原代MSC的替代细胞来源。在iMSC衍生过程中,适当的培养表面可能会影响其生长和分化潜能。本研究通过衍生于明胶或胶原蛋白包被的表面,比较了衍生的小鼠iPS-MSC的分子特性和分化潜能。通过一步法衍生细胞并表达CD73和CD90,但CD105在仅在明胶包被的平板上培养的iMSC中表达下调,且传代次数增加。配对散点分析显示,明胶和胶原表面上的iMSC以及原代小鼠骨髓MSC中MSC特异性基因的表达相似。在明胶和胶原蛋白上衍生iMSCs分别决定了它们的成骨和脂肪分化潜能。在诱导成骨或脂肪分化之前,在明胶上衍生的iMSCs上调了Bmp2和Lif,而通过衍生胶原蛋白则上调了PPARγ。我们的结果表明,细胞外基质成分(例如明胶偏差)通过这些主基因的上调或下调,在其衍生过程中产生了向脂肪或骨骼组织的iMSC分化潜能。

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