Soluble factors secreted by differentiating embryonic stem cells stimulate exogenous cell proliferation and migration.

Soluble factors secreted by differentiating embryonic stem cells stimulate exogenous cell proliferation and migration.
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DOI:
10.1186/scrt415
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发表时间:
2014-02-24
影响因子:
7.5
通讯作者:
McDevitt TC
McDevitt TC
中科院分区:
医学2区
文献类型:
--
作者:
Ngangan AV;Waring JC;Cooke MT;Mandrycky CJ;McDevitt TC

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干细胞作为组织再生的催化剂正在被研究,以直接替代或促进由于创伤性损伤或退行性疾病而丧失的细胞性。在许多报道中,尽管稳定整合的细胞数量少,但递送或募集到组织重塑部位的细胞的短暂存在总体上有利于功能恢复。这些发现激发了确定从移植细胞分泌的旁分泌因子如何能够积极影响内源性修复过程和体细胞反应的需要。胚胎干细胞在体外分化为胚状体(EBs),并在不同的时间间隔收集EBs的条件培养基。通过聚合酶链反应和酶联免疫吸附测定分析,分别作为时间的函数,几种不同的生长因子分泌的EB的基因和蛋白质表达分析进行了研究。用EB条件培养基处理的成纤维细胞和内皮细胞的增殖和迁移与非条件培养基和生长培养基对照相比进行了检查。在胚胎干细胞(ESC)分化为EB的过程中,骨形态发生蛋白4(BMP-4)、胰岛素样生长因子(IGF-1)和血管内皮生长因子(VEGF-A)等多种生长因子的表达增加。根据5-溴-2 ′-脱氧尿苷掺入法和transwell法,分别从不同分化阶段的EB收集的条件培养基刺激成纤维细胞和内皮细胞的增殖和迁移。总的来说,这些结果表明,随着时间的推移,分化中的ESC表达增加量的各种生长因子,这些生长因子共同能够刺激外源性细胞群的促有丝分裂和促运动活性。
Stem cells are being investigated as catalysts of tissue regeneration to either directly replace or promote cellularity lost as a result of traumatic injury or degenerative disease. In many reports, despite low numbers of stably integrated cells, the transient presence of cells delivered or recruited to sites of tissue remodeling globally benefits functional recovery. Such findings have motivated the need to determine how paracrine factors secreted from transplanted cells may be capable of positively impacting endogenous repair processes and somatic cell responses. Embryonic stem cells were differentiated as embryoid bodies (EBs) in vitro and media conditioned by EBs were collected at different intervals of time. Gene and protein expression analysis of several different growth factors secreted by EBs were examined by polymerase chain reaction and enzyme-linked immunosorbent assay analysis, respectively, as a function of time. The proliferation and migration of fibroblasts and endothelial cells treated with EB conditioned media was examined compared with unconditioned and growth media controls. The expression of several growth factors, including bone morphogenic protein-4, insulin-like growth factors and vascular endothelial growth factor-A, increased during the course of embryonic stem cell (ESC) differentiation as EBs. Conditioned media collected from EBs at different stages of differentiation stimulated proliferation and migration of both fibroblasts and endothelial cells, based on 5-bromo-2′-deoxyuridine incorporation and transwell assays, respectively. Overall, these results demonstrate that differentiating ESCs express increasing amounts of various growth factors over time that altogether are capable of stimulating mitogenic and motogenic activity of exogenous cell populations.
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