Retinoic Acid-induced Differentiation of Rat Mesenchymal Stem Cells into β-Cell Lineage

Backgrounds: Type I diabetes mellitus (T1DM), an autoimmune disease, is associated with insulin deficiency due to the death of β-cells. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are capable of tissue repair and thus are a promising source of β-cell surrogates. Methods: In this study, the therapeutic potential of BM-MSCs as β-cell replacements was analyzed both in vitro and in vivo. First, we used retinoic acid (RA) to induce rat BM-MSCs to differentiate into cells of endodermal/pancreatic lineage. Then, differentiated rat BM-MSCs were syngeneically injected under the renal capsule of rats. Results: Analysis of gene expression revealed that rat BM-MSCs showed signs of early pancreatic development, and differentiated cells were qualitatively and quantitatively confirmed to produce insulin in vitro. In vivo study was performed for short-term (3 weeks) and long-term (8 weeks) period of time. Rats that were injected with differentiated MSCs exhibited a reduction in blood glucose levels throughout 8 weeks, and grafted cells survived in vivo for at least 3 weeks. Conclusions: These findings show that RA can induce differentiation of MSCs into the β-cell lineage and demonstrate the potential of BM-MSCs to serve as therapeutic tools for T1DM.ope