Programming of human endometrial-derived stromal cells (EnSCs) into pre-oligodendrocyte cells by overexpression of miR-219

Abstract

Oligodendrocytes are myelinating cells in the central nervous system that form the myelin sheath of axons to support rapid nerve conduction. MicroRNAs have critical roles in oligodendrocyte development. Several studies have shown that miR-219 is necessary to promote oligodendrocyte differentiation through repressing negative regulators of oligodendrocyte development. Human endometrial-derived stromal cells (EnSCs) are abundant and available adult stem cells with low immunological incompatibility, which could be considered for cell replacement therapy in future. After induction of EnSCs by FGF2, EGF and PDGF-AA, they were infected by miR-219-GFP-expressing lentiviruses. The cells were analyzed for expression of stage-specific oligodendrocyte cells markers. Quantitative RT-PCR and immunocytochemistry analyses showed that stage-specific markers Nestin, Olig2, Sox10, PDGFRa, CNP, A2B5, O4, and MBP are expressed in their specific stages through differentiation protocol. Results showed that expression of pre-oligodendrocyte markers in miR-219-GFP-expressing cells were higher than triiodothyronine (T3) treated cells. In conclusion, the EnSCs could be programmed into pre-oligodendrocyte cells by overexpression of miR-219, and may convince to consider these cells as safe source for cell replacement therapy of neurodegenerative diseases.