Generation of Human-induced Pluripotent Stem Cells Derived From Dermal Fibroblast of Schizophrenic Patients.

Abstract

Schizophrenia (SCZ) is a psychiatric disorder caused by environmental, social, and genetic factors. This phenomenon is a severe neuropsychiatric disorder with a 1% worldwide prevalence. As SCZ is an exclusively human disorder, animal models cannot mimic SCZ pathophysiology. Thus, it is crucial to develop a novel human-based specific model of SCZ to elucidate mechanisms of the occurrence of the disease. In this regard, the aim of this study was reprogramming somatic cells to human-induced pluripotent stem cells (hiPSCs), with possible potency to transformed to specific neural stem cells. In the present study, we directly reprogrammed the isolated human ear dermal fibroblasts (HDFs) from schizophrenic patients into hiPSCs using some episomal agents in Matrigel-coated plates. The existence of pluripotency markers was confirmed by the immunocytochemistry (ICC) test and alkaline phosphatase protocol. We performed karyotype analysis to ensure the maintenance of the normal chromosomes. Analysis of colonies exhibited intense alkaline phosphatase engagement and Oct4, SSEA4, Nanog, and Tra-1-60. HiPSCs showed normal karyotypes and were potent to differentiate into ectoderm, endoderm, and mesoderm. This study showed human dermal mesenchymal fibroblasts taken from schizophrenic patients can be reprogrammed to hiPSCs, with potential to transformation to three germ layers with sufficient expression of relate molecular markers. This is the first steps to produce SCZ specific neural stem cells, which can be used in the assessment of cellular changes in schizophrenia and possible effects of antipsychotic agents. .