Neuroectodermally converted human mesenchymal stromal cells provide cytoprotective effects on neural stem cells and inhibit their glial differentiation

Background aimsIn recent years, bone marrow (BM)-derived mesenchymal stromal cells (MSC) have become a promising source for neuroregenerative therapies. We evaluated the trophic effects of neuroectodermally converted MSC (mNSC) on neural stem cells (NSC).MethodsWe quantified the expression of growth factors by mNSC using real-time reverse transcription–polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) and studied the effects of mNSC conditioned medium and mNSC (in direct co-culture) on NSC proliferation, differentiation and survival.ResultsNeuroectodermal conversion of human MSC induced high expression of growth factors at both mRNA and protein levels, most prominently hepatocyte growth factor, vascular endothelial growth factor and amphiregulin (37 ± 17, 92 ± 44 and 12 ± 11 ng/105 cells, respectively), which remained at high levels upon co-culturing with neural cells. Accordingly, mNSC conditioned medium and co-cultivation with mNSC reduced cell death of NSC (36% of control), stimulated their proliferation, attenuated glial differentiation of NSC (7 ± 3 versus 59 ± 6%; P < 0.01) and protected NSC against the neurotoxin 6-hydroxydopamine (with half-maximally concentrations EC50 values of 217 ± 207 μm in the presence of mNSC compared with 62 ± 49 μm for NSC alone).ConclusionsmNSC promote survival and proliferation, and inhibit glial differentiation, of NSC. Protection of NSC by mNSC against 6-hydroxy-dopamine is probably mediated by the release of cytotrophic factors. Our results promote neuroectodermally converted MSC as promising candidate cells for the development of neuroregenerative and neuroprotective therapies.