Generation of insulin-producing hepatocyte-like cells from human Wharton's jelly mesenchymal stem cells as an alternative source of islet cells
Abstract
Islet cell transplantation, as a treatment of type 1 diabetes, has a lot of complexity such as allograft rejections and an insufficient number of donors. The liver can be used as a replacement for endogenous insulin production. Hepatocytes can inherently respond to glucose levels and secrete proteins. Utilization of mesenchymal stem cells for curing diabetes represents a major focus of recent investigations. As a new choice for transplantation, we have proposed glucose-regulated insulin-producing hepatocyte-like cells, which produce insulin dependent on glucose levels. We have transfected human Wharton's jelly mesenchymal stem cells with the special construct, which included homology arms and glucose-responsive elements upstream of the minimum liver-type pyruvate kinase promoter-directed insulin gene. Then, we have differentiated these transfected cells to hepatocyte-like cells by using serial exposure of different inducing material and exogenous growth factors. Immunofluorescence analyses have demonstrated the expression of albumin, cytokeratin-18, Hep-Par1, α-fetoprotein, and insulin. The expression of hepatocyte marker genes in the differentiated cells was confirmed by reverse-transcription polymerase chain reaction. Interes...Continue Reading
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