Basic fibroblast growth factor is a key factor that induces bone marrow mesenchymal stem cells towards cells with Schwann cell phenotype

Abstract

Bone marrow mesenchymal stem cells (MSCs) can be differentiate towards a Schwann cells (SCs) lineage when exposed to pre-inducing reagents β-mercaptoethanol (BME) and retinoic acid (RA), followed by inducing factors: forskolin (FSK), basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF), and heregulin (HRG). However, the underlying mechanisms remain unclear. Here, we investigated the individual effects of these inducing factors on the differentiation of MSCs towards SC phenotype in rats. We show that the omission of either HRG or PDGF from the induction medium is not sufficient to change the SC-like phenotype or the expression level of the SC marker, S100β. However, the omission of bFGF from the induction medium effectively blocked neural induction of the MSCs. Moreover, only bFGF was found to inhibit MSC proliferation during differentiation. To clarify the mechanism responsible for the effect of bFGF, we also investigated the activation of the extracellular signal-regulated kinase (ERK) pathway in the induced cells. Our results suggest that morphological changes in MSCs induced by bFGF depend on the activation of ERK, and bFGF may be an indispensable factor that induces MSCs to differentiate into cells with SCs phenotype.

Keywords: BME; Basic fibroblast growth factor; Bone marrow mesenchymal stem cells; ERK1/2; FSK; HRG; MAPK; MSCs; PDGF; RA; SCs; Schwann cell-like differentiation; Schwann cells; bFGF; basic fibroblast growth factor; bone marrow mesenchymal stem cells; forskolin; heregulin; mitogen-activated protein kinase; platelet derived growth factor; retinoic acid; β-mercaptoethanol.