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Research Article - Asian Journal of Biomedical and Pharmaceutical Sciences (2021) Volume 11, Issue 83
Evaluation of reprogramming mscs by lentivirus harboring ngn3 to produce insulin-secreting cells.
Neurogenin 3 (NGN3) is critical transcription factor that expressed by a population of progenitor cells for developing pancreas and it is alone sufficient to differentiation of pancreatic epithelial cells to islet cells. One of the multipotent stem cell of mesodermal origin is Mesenchymal Stem Cells (MSCs) that can be converted into different cell types; Therefore Reprogramming of these cells can be created insulin-producing cells. NGN3 protein is transiently expressed by exocrine cells undergoing reprogramming to an endocrine cell fate. One of the Major tools for gene delivery in mammalian cells is Lentiviral vectors that have stable expression and ability to mediate potent transduction in mammalian cells both in vitro and in vivo. In this study, lentivirus harboring NGN3 has been used for persistence gene expression in MSC. The idea of this research was to evaluate the expression of the NGN3 gene in MSCs in order to investigate the unique role of NGN3 and the lentivirus to introduce to produce insulin-secreting cells and apply it for gene therapy of hyperglycemia in diabetic rats. MSCs were transducted by lentivirus contain NGN3 gene and expressions of neurogenin3 and insulin gene were confirmed by RT-PCR and western blotting. NGN3 as a master regulator expressed in little percentage of cells within pancreas development functions as a primary activator which directly enhances the expression of the transcription factors involved differentiation of the endocrine progenitor cells into each of the endocrine cell subtypes. The MSCs transfected by lentivirus contain NGN3 gene were secreted insulin 1.1-fold higher in the high-glucose medium than the low-glucose medium. These cells implanted into diabetic rats then the blood glucose level was measured at 0 and 3 days. The results demonstrated a decrease in blood glucose level; therefore, the MSCs transfected with lentivirus contain NGN3 gene can be used as a cell-based gene therapy method for treatment of type 1 diabetes.
Author(s): Samira Talebi, Fathollah Ahmadpour , Teresa May B. Bandiola