Int J Med Sci 2019; 16(12):1668-1676. doi:10.7150/ijms.36011

Research Paper

Direct differentiation of insulin-producing cells from human urine-derived stem cells

Yongha Hwang1*, Seon-Heui Cha2*, Yeonhee Hong1, Ae Ryang Jung3, Hee-Sook Jun1,3,4✉

1. College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, 21999, Republic of Korea
2. Department of Marine Bioindustry, Hanseo University, Chungcheongman-do, 31962, Republic of Korea
3. Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 21936, Republic of Korea
4. Gachon Medical Research Institute, Gil Hospital, Incheon, 21999, Republic of Korea
*These authors contributed equally to this work.

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Citation:
Hwang Y, Cha SH, Hong Y, Jung AR, Jun HS. Direct differentiation of insulin-producing cells from human urine-derived stem cells. Int J Med Sci 2019; 16(12):1668-1676. doi:10.7150/ijms.36011. Available from http://www.medsci.org/v16p1668.htm

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Abstract

The loss of pancreatic β-cells is a cause of diabetes. Therefore, replacement of pancreatic β-cells is a logical strategy for the treatment of diabetes, and the generation of insulin-producing cells (IPCs) from stem cells has been widely investigated as an alternative source for pancreatic β-cells. Here, we isolated stem cells from human urine and investigated their differentiation potential into IPCs. We checked the expression of surface stem cell markers and stem cell transcription factors, and found that the isolated human urine-derived stem cells (hUDSCs) expressed the stem cell markers CD44, CD90, CD105 and stage-specific embryonic antigen (SSEA)-4. In addition, these cells expressed octamer binding transcription factor (Oct)4 and vimentin. hUDSCs could differentiate into adipocytes and osteocytes, as evidenced by Oil-red O staining and Alizarin Red S-staining of differentiated cells, respectively. When we directly differentiated hUDSCs into IPCs, the differentiated cells expressed mRNA for pancreatic transcription factors such as neurogenin (Ngn)3 and pancreatic and duodenal homeobox (Pdx)1. Differentiated IPCs expressed insulin and glucagon mRNA and protein, and these IPCs also secreted insulin in response to glucose stimulation. In conclusion, we found that hUDSCs can be directly differentiated into IPCs, which secrete insulin in response to glucose.

Keywords: urine-derived stem cell, diabetes, differentiation of insulin producing cell, pancreatic beta-cell