Retinoic Acid-induced Differentiation of Rat Mesenchymal Stem Cells into beta-Cell Lineage.
10.4285/jkstn.2015.29.3.118
- Author:
Jae Hyung KIM
1
;
Kyung Sik KIM
;
Sang Woo LEE
;
Hyun Woo KIM
;
Dong Jin JOO
;
Yu Seun KIM
;
Hwal SUH
Author Information
1. Graduate Program of Nano Science and Technology, Graduate School of Yonsei University, Seoul, Korea. yukim@yuhs.ac, hwal@yuhs.ac
- Publication Type:In Vitro ; Original Article
- Keywords:
Type 1 diabetes mellitus;
Insulin-secreting cells;
Mesenchymal stromal cells;
Tretinoin;
Insulin
- MeSH:
Animals;
Autoimmune Diseases;
Blood Glucose;
Diabetes Mellitus;
Diabetes Mellitus, Type 1;
Gene Expression;
Insulin;
Insulin-Secreting Cells;
Mesenchymal Stromal Cells*;
Rats*;
Transplants;
Tretinoin
- From:The Journal of the Korean Society for Transplantation
2015;29(3):118-129
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUNDS: Type I diabetes mellitus (T1DM), an autoimmune disease, is associated with insulin deficiency due to the death of beta-cells. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are capable of tissue repair and thus are a promising source of beta-cell surrogates. METHODS: In this study, the therapeutic potential of BM-MSCs as beta-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 beta-cell lineage and demonstrate the potential of BM-MSCs to serve as therapeutic tools for T1DM.
