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Exploiting human CD34+ stem cell-conditioned medium for tissue repair

机译:利用人类CD34 +干细胞条件培养基进行组织修复

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Despite the progress in our understanding of genes essential for stem cell regulation and development, little is known about the factors secreted by stem cells and their effect on tissue regeneration. In particular, the factors secreted by human CD34 + cells remain to be elucidated. We have approached this challenge by performing a cytokine/growth factor microarray analysis of secreted soluble factors in medium conditioned by adherent human CD34 + cells. Thirty-two abundantly secreted factors have been identified, all of which are associated with cell proliferation, survival, tissue repair, and wound healing. The cultured CD34 + cells expressed known stem cell genes such as Nanog, Oct4, Sox2, c-kit, and HoxB4. The conditioned medium containing the secreted factors prevented cell death in liver cells exposed to liver toxin in vitro via inhibition of the caspase-3 signaling pathway. More importantly, in vivo studies using animal models of liver damage demonstrated that injection of the conditioned medium could repair damaged liver tissue (significant reduction in the necroinflammatory activity), as well as enable the animals to survive. Thus, we demonstrate that medium conditioned by human CD34 + cells has the potential for therapeutic repair of damaged tissue in vivo.
机译:尽管我们对干细胞调节和发育必不可少的基因的理解有所进步,但对干细胞分泌的因子及其对组织再生的影响知之甚少。特别是,人类CD34 +细胞分泌的因子仍有待阐明。我们通过对粘附的人CD34 +细胞条件下的培养基中分泌的可溶性因子进行细胞因子/生长因子微阵列分析来应对这一挑战。已鉴定出32种高度分泌的因子,所有这些因子均与细胞增殖,存活,组织修复和伤口愈合有关。培养的CD34 +细胞表达已知的干细胞基因,例如Nanog,Oct4,Sox2,c-kit和HoxB4。含有分泌因子的条件培养基可通过抑制caspase-3信号传导途径,防止在体外暴露于肝毒素的肝细胞死亡。更重要的是,使用肝损伤动物模型进行的体内研究表明,条件培养基的注射可以修复受损的肝组织(坏死性炎症活性明显降低),并使动物得以生存。因此,我们证明了以人CD34 +细胞为条件的培养基具有在体内修复受损组织的潜力。

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