Radhika Shah

Introduction. Diabetes mellitus is a chronic disease in which the level of glucose in the blood cannot be maintained. Type I diabetes manifests as an autoimmune disorder, in which the patient’s immune system attacks the insulin-producing beta cells of the pancreas. When these cells become deficient, insulin production is decreased, and plasma glucose can no longer be controlled, leading to hyperglycemia.¹ The disease is of growing concern, as there is no cure, and it is the seventh leading cause of death in the U.S.² Stem cell treatment of diabetes could be used to regenerate beta cells of the pancreas. Pdx-1 (Pancreatic and Duodenal Homeobox 1) is a transcription factor involved in development of the pancreas and formation of insulin-producing beta cells. Expression of transcription factors, such as Pdx-1, on stem cells can significantly increase beta cell regeneration.^3,4 Methods. Both in vitro and in vivo methods were utilized. In vitro methods involved transfection of both hiPSCs (human-induced pluripotent stem cells) and ASCs (adipose tissue-derived stem cells) with a virus vector containing Pdx-1. The transfected stem cells were developed using an MEF feeder layer through a 15-day supplementary differentiation process. Specific marker expression, including NGN3 and INS, was observed using immunofluorescence assay and flow cytometry and C-peptide level after glucose exposure was measured through a C-peptide release assay to determine insulin-producing capacity.⁵ In vivo methods implemented a similar in vitro process but injected the differentiated Pdx-1 stem cells into diabetic rats. Rats were induced with hyperglycemia (diabetes) using streptozotocin. Blood glucose levels in the rats were then measured for efficacy of treatment.⁶ Results. The stem cell differentiation process was successful in producing beta-like cells, as the INS (insulin) marker was expressed in immunofluorescence assay at day 15 of differentiation. When exposed to glucose, C-peptide levels, indicative of insulin production, were significantly increased in Pdx-1 stem cells compared to undifferentiated cells.⁵ In the diabetic rats, hyperglycemia was markedly reduced, shown by a decrease in fasting blood glucose levels compared to the diabetic rats not injected with Pdx-1 stem cells.⁶ Conclusions. By inducing overexpression of Pdx-1, a vital marker in pancreatic development, in diabetic patient-derived stem cells, beta cells can be regenerated to produce insulin and lower blood glucose levels. Although research on stem cell therapy in the disease process of diabetes mellitus is relatively new, the field shows to be promising based on the positive results seen in these studies.

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2. “National Center for Health Statistics.” Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 03 May 2017. Web. 23 Mar. 2018. <https://www.cdc.gov/nchs/fastats/diabetes.htm>.
3. Kimura A, Toyoda T, Nishi Y, Nasu M, Ohta A, and Osafune K. Small molecule AT7867 proliferates PDX1-expressing pancreatic progenitor cells derived from human pluripotent stem cells, Stem Cell Research. 2017;24;61-68.
4. Van der Meulen T, Huising MO. The role of transcription factors in the transdifferentiation of pancreatic islet cells. Journal of molecular endocrinology. 2015;54(2):R103-R117.
5. Rajaei B, Shamsara M, and Sanati, MH. In Vitro Generation of Glucose-Responsive Insulin-Secreting Cells from Pancreatic and Duodenal Homeobox 1-Overexpressing Human-Induced Pluripotent Stem Cell Derived from Diabetic Patient, ASAIO Journal. 2017;1-8.
6. Tabar MH, Tabandeh MR, Moghimipour E, Dayer D, Ghadiri AA, Bakhshi EA, Orazizadeh M, and Ghafari MA. The combined effect of Pdx1 overexpression and Shh manipulation on the function of insulin-producing cells derived from adipose-tissue stem cells, FEBS Open Bio. 2018;8:372-382.