Transplantation of human pluripotent stem cells overexpressing ERRγ can efficiently improve the symptoms of type 2 diabetes patient

aihua Wang
2018 Advances in Tissue Engineering & Regenerative Medicine Open Access  
Abbreviations: hESCs, human embryonic stem cells; hiPSCs, human induced pluripotent stem cells; ERRγ, estrogen-related receptor γ; hADSCs, human adipose-derived stem cells; dgHPSCs: directly generated human pluripotent stem cells Estrogen-related receptor γ (ERRγ) is a master regulator of β cell maturation in vivo. Forced expression of ERRγ in hiPSC-derived β-like cells enables glucose-responsive secretion of human insulin in vitro, and can further restore the glucose homeostasis in type 1
more » ... tes mouse models after transplantation, without the need for kidney capsule maturation, to achieve functionality immediately. 16 Human adipose-derived stem cells (hADSCs) were first confirmed by Zuk et al., 17 to have the potentials to differentiate toward the osteogenic, adipogenic, myogenic, chondrogenic, and putative neurogenic cells. Sun et al. 18 reported the successful induction of hiPSCs from hADSCs with lentivirus transduction containing human Oct4, Sox2, Klf4, and c-MYC. 18 Yet the use of oncogene c-MYC as one of the inducing factors still remained to be a potential concern for the clinical application of these hADSC-derived iPSCs. During the past years, we invented a novel protocol, which can directly generate human pluripotent stem cells from hADSCs without Adv Tissue Eng Regen Med Open Access. 2018;4(3):50-55. 50 Abstract Since the discovery that insulin can reduce blood glucose levels in 1922, exogenous insulin administration becomes the standard method to treat human diabetes patients. Yet, this method cannot efficiently prevent the development of diabetes complications. Here, we report a combinatorial strategy that combines human pluripotent stem cells and overexpression of estrogen-related receptor γ (ERRγ) together, which, in theory, not only can repair the damaged tissues and restore the function of human pancreatic β cells, but also can synthesize and secrete human insulin, so that to reduce the blood glucose levels of the diabetic patients after transplantation. Our preliminary investigation demonstrated that our method can efficiently secrete human insulin, increase the secretion of human C-peptide, and improve the patient's health conditions physically and mentally, thus, with the potential to prevent and even to reverse human diabetic complications with more transplantations. Our reports laid an important foundation for treating human diabetes and eventually cure this disease.
doi:10.15406/atroa.2018.04.00078 fatcat:rckev2hu3zcyzc2yb6nmysmonu