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

• Type of Material: Article
• Authors: Alyssa V. Ngangan, Georgia Institute of Technology; James C. Waring, Georgia Institute of Technology; Marissa T. Cooke, Georgia Institute of Technology; Christian J. Mandrycky, Georgia Institute of Technology; Todd McDevitt, Emory University
• Language: English
• Date: 2014-02-24
• Publisher: BMC
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Ngangan et al.; licensee BioMed Central Ltd.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://dx.doi.org/10.1186/scrt415
• Title of Journal or Parent Work: Stem Cell Research & Therapy
• Volume: 5
• Issue: 1
• Start Page: 26
• End Page: 26
• Grant/Funding Information: AVN was supported by an NIH Cell & Tissue training grant (T32 GM00843321).; This work was supported by funding from the National Institutes of Health (R21 EB007316), the Atlanta Clinical Translational Science Institute (UL1 RR025008), and the Georgia Tech/Emory Center (GTEC) for the Engineering of Living Tissues Engineering Research Center (EEC 9731463).
• Keywords: Conditioned medium; Bodies; Model; Science & Technology; Cell & Tissue Engineering; Research & Experimental Medicine; Apoptosis; Angiogenesis; Medicine, Research & Experimental; Muscle regeneration; Transplantation; Cell Biology; Gene transfer; In-vitro; Endothelial growth-factor; Life Sciences & Biomedicine
• Research Categories: Biology, Cell; Biology, Molecular; Engineering, Biomedical

Abstract

Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.