Differentiation of Urine-Derived Induced Pluripotent Stem Cells to Neuron, Astrocyte and Microvascular Endothelial Cells from a Diabetic Patient

Abstract

Background: Complications of central nervous system (CNS) in type 2 diabetes mellitus (T2DM) often lead to cognitive impairment and seriously affect the quality of life. However, there is no individualized disease model. Urinary epithelial cells (UECs) can be an ideal source for generating human induced pluripotent stem cells (hiPSCs) and progenitors, as they are easily accessible, non-invasive and universally available. Therefore, we intended to differentiate urine-derived hiPSCs into neuron (N), astrocyte (A) and microvascular endothelial cells (E) from a T2DM patient for future study its pathogenesis and precision medical treatment. Methods and Results: hiPSCs was successfully induced from UECs using integration free Sendai virus technology in a totally noninvasive manner. It had a normal karyotype (46, XY) and were proved to be pluripotent by immunofluorescence staining, alkaline phosphatase staining, karyotyping, teratoma experiments and methylated analysis. N, A and E were successfully induced and displayed typical morphological characteristics. Conclusions: This study indicates that N, A, E can be generated from urine-derived hiPSCs. Then we intend to create a new disease model in vitro to simulate the cerebral microenvironment of DM which will provide new methods for further investigate the disease-specific mechanisms.