qRT-PCR showed the expression of insulin, glucagon, and somatostatin in undifferentiated hPDMSCs and in ILCs

qRT-PCR showed the expression of insulin, glucagon, and somatostatin in undifferentiated hPDMSCs and in ILCs. ILCs. Differentiated ILCs were found to express human insulin, glucagon, and UM-164 somatostatin by immunocytochemistry. Additionally, ILCs also showed abundance of pancreatic transcription factors ngn3 and isl1. Both undifferentiated hPDMSCs and ILCs exihibited insulin secretion in response to glucose. Transplantation of hPDMSCs or ILCs derived from hPDMSCs in STZ-induced diabetic UM-164 mice led to restoration of normoglycemia. Our results demonstrate, for the first time, reversal of hyperglycemia by undifferentiated hPDMSCs and ILCs derived from hPDMSCs. These results suggest human placenta-derived MSCs as an alternative source for cell replacement therapy in diabetes. Keywords:human placenta-derived stem cell, diabetes, mesenchymal stem cell, transplant, beta-cell, islet, differentiation, macrocapsule, immunoisolation == Introduction == Diabetes mellitus is becoming one of the main threats to human health in the 21st century [1]. The global prevalence of diabetes is shifting significantly from the developed countries to the developing countries [2]. Beta-cell replacement is an effective treatment for type 1 diabetes, but its applicability is limited by the lack of sufficient donor tissue, raising the need for alternative tissue sources. Human embryonic stem cells (hESCs) have received much attention in the last few years because of their promise as a renewable source of tissue for beta-cell differentiation [3]. However, ethical issues surrounding the use of hESCs limit its use in clinical application of cell replacement therapy. Also, tissue-resident stem cells have demonstrated self-renewal and multipotent differentiation potential, which could be of great value for the successful progress of cellular therapies for diabetes. The placenta is a temporary organ that accompanies pregnancy connected to the fetus via the umbilical cord. Besides playing a fundamental and essential role in fetal development, nutrition, and tolerance, placenta may UM-164 also represent a reserve of progenitor/stem cells. Recently, the placenta was shown to be an important hematopoietic organ, containing cells in chorionic villi that showed hematopoietic cell lineage UM-164 differentiation along with presence of the hematopoietic markers CD34 and CD45 [4]. In addition to hematopoietic stem cells, the placenta has been reported to contain a population of multipotent stem cells exhibiting some of the characteristics of pluripotent ESCs including expression of stem cell markers c-kit, Thy-1, oct-4, SOX2, hTERT, SSEA-1, SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81 [5]. These cells resemble mesenchymal stem cells and can be induced to differentiate into hepatocyte, vascular endothelial, cartilage, and VCA-2 neural-like cells [5-16]. Differentiation of these human placenta-derived mesenchymal stem cells (hPDMSCs) into insulin positive cells [17,18] has raised hopes for the use of these cells as an alternative source for cell therapy in diabetes. It is known that Insulin is the only gene that is imprinted exclusively in UM-164 the yolk sac placenta [19]. The yolk sac placenta and the pancreas of both human and mouse are the only tissues that produce insulin [20-22]. Rodent yolk sac is a known major source of insulin imprint [19,20,23], which starts by day 14.5 [24]. This suggests that yolk sac placental imprinting of insulin is an ancestral trait [25]. However, mechanisms for regulating insulin gene expression in placental tissue differ from those in pancreatic beta-cells [23]. Based on these findings, we hypothesized that hPDMSCs retaining imprinted insulin may act as surrogate beta-cells. Therefore, we supposed it is likely that transplantation of hPDMSCs under the kidney capsule of experimental diabetic mice may help to reduce hyperglycemia through insulin secretion. MSCs from bone marrow and placenta share similar characteristics, and possess immunomodulatory properties. Both have been.