Co-overexpression of GDNF and GFRalpha1 induces neural differentiation in neural progenitor cells in comparison to bone marrow stromal cells

Abstract

Neural progenitor cells (NPCs) and bone marrow stromal cells (BMSCs), both of which can differentiate into neural phenotypes, are important candidates for transplantation therapy in the central nervous system (CNS). In most cases of BMSC transplantation, functional recovery is recognized even if few transplanted cells survive in the host tissue. A reason for this may be that transplanted cells produce neurotrophic factors (NFs), which enhance neuronal survival and neurite outgrowth after CNS injury. To provide additional insight into cell therapy, we investigated the types of NFs and receptors that are expressed in NPCs and BMSCs in vitro. Both cells expressed the mRNA of nerve growth factor (NGF), cilliary neurotrophic factor (CNTF), glial cell line-derived neurotrophic factor (GDNF), and their receptors in the proliferative state. Real-time PCR analysis showed that mRNA expression of GDNF was relatively low in NPCs although its receptor was highly expressed. We thus tested if the overexpression of GDNF in NPCs affected neural differentiation without FGF-2. The overexpression of GDNF did not affect mRNA expression of beta-III tubulin and neuron specific enolase (NSE), but both GDNF and GFRalpha1 overexpression increased the expression of neuronal markers. These results suggest that augmentation of both GDNF and GFRalpha1 could have positive effects during neural tissue repair.