Mouse Anti Rat Nkx6.1 Hybridoma [G75B7C5]

Human pluripotent stem cells (hPSCs) represent a renewable source of pancreatic beta cells for both basic research and therapeutic applications. Given this outstanding potential, significant efforts have been made to identify the signaling pathways that regulate pancreatic development in hPSC differentiation cultures. In this study, we demonstrate that the combination of epidermal growth factor (EGF) and nicotinamide signaling induces the generation of NKX6-1(+) progenitors from all hPSC lines tested. Furthermore, we show that the size of the NKX6-1(+) population is regulated by the duration of treatment with retinoic acid, fibroblast growth factor 10 (FGF10), and inhibitors of bone morphogenetic protein (BMP) and hedgehog signaling pathways. When transplanted into NOD scid gamma (NSG) recipients, these progenitors differentiate to give rise to exocrine and endocrine cells, including monohormonal insulin(+) cells. Together, these findings provide an efficient and reproducible strategy for generating highly enriched populations of hPSC-derived beta cell progenitors for studies aimed at further characterizing their developmental potential in vivo and deciphering the pathways that regulate their maturation in vitro.

A physio-pathological feature of diabetes mellitus is a significant reduction of beta-pancreatic cells. The growth, differentiation and function maintenance of these cells is directed by transcription factors. Nkx6.1 is a key transcription factor for the differentiation, neogenesis and maintenance of beta-pancreatic cells. We reported that silymarin restores normal morphology and endocrine function of damaged pancreatic tissue after alloxan-induced diabetes mellitus in rats. The aim of this study was to analyze the effect of silymarin on Nkx6.1 transcription factor expression and its consequence in beta cells neogenesis. Sixty male Wistar rats were partially pancreatectomized and divided into twelve groups. Six groups were treated with silymarin (200 mg/Kg p.o) for periods of 3, 7, 14, 21, 42 and 63 days. Additionally, an unpancreatectomized control group was used. Nkx6.1 and insulin gene expression were assessed by RT-PCR assay in total pancreatic RNA. beta-Cell neogenesis was determined by immunoperoxidase assay. Silymarin treated group showed an increase of Nkx6.1 and insulin genic expression. In this group, there was an increment of beta-cell neogenesis in comparison to pancreatectomized untreated group. Silymarin treatment produced a rise in serum insulin and serum glucose normalization. These results suggest that silymarin may improve the reduction of beta pancreatic cells observed in diabetes mellitus.