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KMID : 0361120150290030118
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Korean Journal of Transplantation
2015 Volume.29 No. 3 p.118 ~ p.129
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Retinoic Acid-induced Differentiation of Rat Mesenchymal Stem Cells into β-Cell Lineage
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Kim Jae-Hyung
Kim Kyung-Sik
Lee Sang-Woo
Kim Hyun-Woo
Joo Dong-Jin
Kim Yu-Seun
Suh Hwal
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Abstract
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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.
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KEYWORD
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Type 1 diabetes mellitus, Insulin-secreting cells, Mesenchymal stromal cells, Tretinoin, Insulin
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