Introduction: Stem cells are being investigated as catalysts of tissue regeneration to either directly replace or\r\npromote cellularity lost as a result of traumatic injury or degenerative disease. In many reports, despite low\r\nnumbers of stably integrated cells, the transient presence of cells delivered or recruited to sites of tissue\r\nremodeling globally benefits functional recovery. Such findings have motivated the need to determine how\r\nparacrine factors secreted from transplanted cells may be capable of positively impacting endogenous repair\r\nprocesses and somatic cell responses.\r\nMethods: Embryonic stem cells were differentiated as embryoid bodies (EBs) in vitro and media conditioned by EBs\r\nwere collected at different intervals of time. Gene and protein expression analysis of several different growth factors\r\nsecreted by EBs were examined by polymerase chain reaction and enzyme-linked immunosorbent assay analysis,\r\nrespectively, as a function of time. The proliferation and migration of fibroblasts and endothelial cells treated with\r\nEB conditioned media was examined compared with unconditioned and growth media controls.\r\nResults: The expression of several growth factors, including bone morphogenic protein-4, insulin-like growth factors\r\nand vascular endothelial growth factor-A, increased during the course of embryonic stem cell (ESC) differentiation\r\nas EBs. Conditioned media collected from EBs at different stages of differentiation stimulated proliferation and\r\nmigration of both fibroblasts and endothelial cells, based on 5-bromo-2'-deoxyuridine incorporation and transwell\r\nassays, respectively.\r\nConclusions: Overall, these results demonstrate that differentiating ESCs express increasing amounts of various\r\ngrowth factors over time that altogether are capable of stimulating mitogenic and motogenic activity of exogenous\r\ncell populations.
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