OBJECTIVETo explore the effects of rhEPO on the migration of bone marrow(BM) derived mesenchymal stem cells(MSCs) and its probable signal transduction mechanism.

METHODSMSC was cultured by classical whole BM adherence method; MSC characteristics was identified by multi-differentiation and surface marker (CD90, CD133, CD34, CD105). The effect of different concentrations EPO (1, 10, 100, 1000 IU/ml) on MSCs migration were observed. Then 30 minutes later, MSC were treated with signal transduction pathway inhibitors, 50 nmol/L wortmannin, 50 micromol/L PD98059, 10 micromol/L U73122, 4 microg/ml Anti EPO-R IgG, 30 micromol/L SB203580, 10 mmol/L Staurosporine, 6 nmol/L G06976 and 50 micromol/L Pseudo Z, respectively. The efficacy of MSC migration was analyzed by Transwell in vitro migration assay.

RESULTSCultured MSCs had the capacities for osteogenic and adipogenic differentiation and highly expressed CD105, CD90 and EPO-R. The efficiency of MSC in vitro migration increased gradually in a concentration-dependent manner with increasing concentration of rhEPO, and the ability peaked at a concentration of 100 IU/ml. Furthermore, the migration ability was decreased on treated with U73122, Anti EPO-R IgG, Staurosporine, Pseudo Z treatment.

CONCLUSIONEPO/EPO-R-mediated MSCs migration is related with MAPK, PI-PLC/PKC-zeta signal pathways, PKC-zeta signal pathway may be of central role for MSCs migration.