1] Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK [2] Qatar Biomedical Research Institute, Education City, Doha, Qatar.
1] Department of Surgery & Hepatitis Research Center, National Taiwan University Hospital, Taipei City, Taiwan [2] Graduate Institute of Clinical Medicine, National Taiwan University, Taipei City, Taiwan.
Mol Ther. 2014 Jan;22(1):149-59. doi: 10.1038/mt.2013.194. Epub 2013 Aug 28.
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.
尽管我们在理解对干细胞调节和发育至关重要的基因方面取得了进展，但对于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。我们通过对贴壁人类 CD34+细胞条件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解决这一难题。已经鉴定出 32 种大量分泌的因子，所有这些因子都与细胞增殖、存活、组织修复和伤口愈合有关。培养的 CD34+细胞表达了已知的干细胞基因，如 Nanog、Oct4、Sox2、c-kit 和 HoxB4。含有分泌因子的条件培养基通过抑制半胱天冬酶-3 信号通路，防止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的体内研究表明，注射条件培养基可以修复受损的肝组织（显著降低坏死性炎症活动），并使动物存活。因此，我们证明了人类 CD34+细胞的培养基具有在体内治疗性修复受损组织的潜力。
