骨髓间充质干细胞向功能性视网膜色素上皮细胞的诱导分化

PURPOSE To investigate the potential ability of bone marrow mesenchymal stem cells (BMMSCs) differentiation toward a functional retinal pigment epithelium (RPE) cell phenotype. METHODS BMMSCs and RPE cells for Brown Norway rat were isolated and cultured in vitro. BMMSCs were separately co-cultured with RPE cells, or they were exposed to either RPE cell-conditioned medium (RPECM), photoreceptor outer segments (POS), or a combination of RPECM and POS (RPECM-POS). The treated cells were analyzed for morphology and the expression of RPE markers (cytokeratin 8, CRALBP, and RPE65) to assess the RPE differentiation. RESULTS Significantly higher pigment accumulation and increased protein expression of the three markers were seen in cells cultured in RPECM-POS than in other treated cultures. Furthermore, the RPECM-POS-treated cultures displayed ultrastructural features typical of RPE cells, expressed RPE cell functional proteins, and had the capability to phagocytose POS. CONCLUSIONS The combination of RPECM and POS stimulate BMMSCs differentiation toward a functional RPE phenotype. Our results provide the foundation for a new route to RPE regenerative therapy involving BMMSCs. Future work isolating the active agent in RPECM and POS would be useful in therapies for RPE diseases or in developing appropriately pre-differentiated BMMSCs for tissue-engineered RPE reconstruction.