Enhancing trophic support of mesenchymal stem cells by ex vivo treatment with trophic factors

Background: Several studies have examined the enhanced efficacy of mesenchymal stem cells (MSCs) using neurotrophic factor transfection in ischemic rat models. However, gene therapy, e.g., the application of MSCs transfected with neurotrophic factors, is not feasible in clinical practice for ethical reasons. Therefore, we evaluated cultivation with specific trophic factors in an attempt to enhance the efficacy of human MSCs (hMSCs) in ischemic stroke. Methods: Using quantitative sandwich enzyme-linked immunosorbent assay (ELISA), we analyzed the levels of trophic factors released from hMSCs after treatment with ischemic brain extract. Trophic factors were pretreated under ex vivo culture conditions. The concentrations of each trophic factor produced by the trophic factor-pretreated and non-pretreated hMSCs were then measured and compared. Results: hMSCs cultured with ischemic rat brain extract showed increased production of BDNF (brain-derived neurotrophic factor), VEGF (vascular endothelial growth factor) and HGF (hepatocyte growth factor). Ex vivo treatment with trophic factors led to a further increase in the production of the trophic factor by hMSC, suggesting autocrine regulation of hMSCs. The morphology and expression of surface markers of hMSCs were not changed, but the cell viability and cell proliferation ability increased after treatment with trophic factors. Conclusions: Our data indicate that hMSCs provide trophic support to the ischemic brain, which can be enhanced by ex vivo treatment of trophic factors during cultivation of hMSCs.