Schwann cells induce Proliferation and Migration of Oligodendrocyte Precursor Cells Through Secretion of PDGF-AA and FGF-2

Abstract

Our previous study has showed that co-grafted Schwann cells (SCs) promote proliferation and migration of the grafted oligodendrocyte precursor cells (OPCs). However, how the co-grafted SCs affect OPCs has not been clarified. In the present study, we confirmed that SC-induced proliferation and migration of OPCs were mediated by SC-secreted factors using SC-conditioned medium (SCM). Then, we detected several candidate factors, PDGF-AA, FGF-2, and IGF-1, in SCs and SCM, and their receptors in OPCs. Finally, by using the selective inhibitors, the effects of these candidate factors on proliferation and migration of OPCs were examined. Our results showed that SCM-stimulated proliferation and migration of OPCs could be markedly decreased by both AG1295 (the inhibitor of PDGFR) and PD173074 (the inhibitor of FGFR). Together, our study suggests that SCs affect proliferation and migration of OPCs through secreting PDGF-AA and FGF-2. Identity of these molecules not only contributes to understand the mechanism of SC-induced proliferation and migration of OPCs but also provides possible target for treatment of CNS diseases.

Transplantation of PDGF-AA-Overexpressing Oligodendrocyte Precursor Cells Promotes Recovery in Rat Following Spinal Cord Injury

“…Our previous study showed that co-transplantation of SCs and OPCs promoted the survival, proliferation and migration of transplanted OPCs in vivo and improved neurological recovery following SCI (Hu et al, 2013). A subsequent in vitro study confirmed that SCs modulated the proliferation and migration of OPCs by secreting platelet-derived growth factor (PDGF)-AA and fibroblast growth factor-2 (FGF)-2 (Chen et al, 2015); moreover, we showed that PDGF-AA stimulated the proliferation of OPCs and their differentiation into OLs at later stages (Hu et al, 2008). We therefore speculated that PDGF-AA administration would have similar effects as SCs in OPC transplantation for SCI repair.…”

“…As previously mentioned, SCs promote OPC proliferation and migration through secreting PDGF-AA and FGF-2 (Chen et al, 2015). In the present study, we only explored the effect of PDGF-AA-overexpressing OPCs on SCI.…”

“…SCs modulate OPC proliferation and migration via secretion of PDGF-AA and FGF-2 (Chen et al, 2015). In the present study, we investigated whether transplantation of OPCs overexpressing PDGF-AA could improve functional recovery after SCI.…”

To Be or Not to Be: Environmental Factors that Drive Myelin Formation during Development and after CNS Trauma

“…For instance, transient exposure to FGF-2 has no effect on OPC migration, whereas OPCs show long-term migration when exposed to PDGF-A under the same conditions [26]. Treating cells with both growth factors leads to faster migration compared to either alone, and also converts progenitors from slowly to rapidly dividing cells [26,[35][36][37][38]. Similar to PDGF-A, FGF-2 promotes OPC migration via the ERK1/2 signaling pathway after binding to its receptors FGFR1, which is necessary for FGF-2-induced migration [27,37,39,40].…”

Co-transplantation of MRF-overexpressing oligodendrocyte precursor cells and Schwann cells promotes recovery in rat after spinal cord injury

“…Schwann cells (SCs) are peripheral nervous system-derived myelin-forming cells that produce growth-promoting factors and cell adhesion molecules (Acheson et al, 1991;Chiu et al, 1991;Oudega and Xu, 2006). Our previous study showed that SCs induce proliferation and migration of OPCs via secretion of platelet-derived growth factor (PDGF)-AA and fibroblast growth factor (FGF)-2 in vitro (Chen et al, 2015); moreover, co-transplantation of SCs and OPCs promoted survival, proliferation and migration of transplanted OPCs in vivo and improved neurological recovery following SCI (Hu et al, 2013).…”