Differentiation of insulin-producing cells from human cord bloodderived haemopoietic stem cells in vitro

Abstract

The use of stem cells in regenerative medicine holds great promise for the cure of many diseases, including type 1 diabetes mellitus, which, despite of the advances in current therapeutic approaches, remains to be one of the most serious health care problems. In addition to the traditional sources of adult stem cells, human umbilical cord blood has provided an important source of stem cells for research due to its unique advantages compared to other sources. In this study, we aimed at optimizing culture conditions for obtaining insulin-producing cells from cord blood hematopoietic stem cells. Twenty cord blood samples were subjected to short-term, liquid static culture that favors the proliferation of CD34+ hematopoietic stem cells. A duplicate culture was set for each sample, one with high glucose concentration and the other with low glucose concentration. Then these cells were subsequently induced to transdifferentiate into insulin-producing cells via a biphasic liquid culture using exendin-4. The expression of human insulin was then tested using RT-PCR. At the end of the culture, 17 out of the 20 samples (85%) cultured in high glucose concentration showed positive human insulin mRNA expression, while culture media with low glucose concentration failed to induce transdifferentiation into insulin-producing cells in any of the 20 samples. In brief, our study demonstrate that hematopoietic cord blood stem cells can transdifferentiate into insulin-producing cells in short-term liquid culture supplemented with high glucose concentration, nicotinamide, and exendin-4 in vitro.