5-Azacytidine Enhances Differentiation of Human Placenta-derived Mesenchymal Stem Cells Towards Schwann-like Cells

Mesenchymal stem cells (MSCs) can be used for regenerative medicine, particularly in the treatment of neurodegenerative diseases and peripheral nerve injuries. Among these, human placenta-derived mesenchymal stem cells (hPMSCs) possess a high potential for differentiation into various cell types, including those of the neural lineage under appropriate conditions. The primary aim of this study was to isolate and induce the differentiation of hPMSCs into Schwann cell-like cells (SC-like cells) that function to support and play a role in the peripheral nervous system.

Human placental tissues were isolated, and hPMSCs were cultured and characterized. The isolated hPMSCs were positive for mesenchymal stem cell surface markers CD73, CD90, and CD105. The multipotency of hPMSCs was confirmed by their ability to differentiate into osteocytes, chondrocytes, and adipocytes. To induce Schwann cell differentiation, hPMSCs were cultured in Schwann cell differentiation medium with or without the addition of 5-azacytidine (5-aza). Gene and protein expression analyses were performed to assess Schwann cell-specific markers.

After 14 days of induction, hPMSCs differentiated in Schwann cell differentiation medium showed significant upregulation of Schwann cell-specific genes S100β, P75, GFAP, and PMP22 (p<0.01). Interestingly, the group treated with 5-aza exhibited even higher expression levels of these genes compared to the Schwann cell differentiation medium alone and the control group (p<0.01). Furthermore, protein expression analysis demonstrated that glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) were highly expressed in the 5-aza-treated condition, confirming enhanced Schwann cell-like differentiation.

This study demonstrates that hPMSCs can be successfully differentiated into Schwann cell-like cells. The addition of 5-aza significantly promoted this differentiation, leading to higher expression of Schwann cell-specific genes and proteins. These findings suggest that 5-aza plays a supportive role in enhancing Schwann cell differentiation from hPMSCs and may provide a promising approach for future clinical applications in peripheral nerve regeneration.