BACKGROUND AND OBJECTIVES: Type 1 Diabetes Mellitus (T1DM) is an autoimmune disorder resulting out of T cell mediated destruction of pancreatic beta cells. Immunomodulatory properties of mesenchymal stem cells may help to regenerate beta cells and/or prevent further destruction of remnant, unaffected beta cells in diabetes. We have assessed the ability of umbilical cord derived MSCs (UCMSCs) to differentiate into functional islet cells in vitro. METHODS AND RESULTS: We have isolated UCMSCs and allowed sequential exposure of various inducing agents and growth factors. We characterized these cells for confirmation of the presence of islet cell markers and their functionality. The spindle shaped undifferentiated UCMSCs, change their morphology to become triangular in shape. These cells then come together to form the islet like structures which then grow in size and mature over time. These cells express pancreatic and duodenal homeobox -1 (PDX-1), neurogenin 3 (Ngn-3), glucose transporter 2 (Glut 2) and other pancreatic cell markers like glucagon, somatostatin and pancreatic polypeptide and lose expression of MSC markers like CD73 and CD105. They were functionally active as demonstrated by release of physiological insulin and C-peptide in response to elevated glucose concentrations. CONCLUSIONS: Pancreatic islet like cells with desired functionality can thus be obtained in reasonable numbers from undifferentiated UCMSCs in vitro. This could help in establishing a "very definitive source" of islet like cells for cell therapy. UCMSCs could thus be a game changer in treatment of diabetes.
C-Peptide ; Cell- and Tissue-Based Therapy* ; Diabetes Mellitus, Type 1 ; Genes, Homeobox ; Glucagon ; Glucose ; Glucose Transport Proteins, Facilitative ; Insulin* ; Insulin-Secreting Cells ; Intercellular Signaling Peptides and Proteins ; Islets of Langerhans ; Mesenchymal Stromal Cells* ; Pancreatic Polypeptide ; Somatostatin ; Stem Cells ; Umbilical Cord*

A putative polypeptide hormone identified as amylin[islet amyloid polypeptide] is synthesized and co-localized with insulin in B cells of pancreatic islets in several animal species including man. However, there is growing evidence that somatostatin cells are also expressed and contained amylin in the pancreatic islets of the rat The aim of the present study was to investigate the immunocytochemical expression of the amylin within the endocrine pancreas of the man, rabbit and guinea pig, with special reference to the possible ability of islet cells other than insulin cells to synthesize amylin. For this purpose serial sections of the pancreatic islets were stainedimmunocytochemically using anti-amylin, anti-insulin, anti-glucagon, anti-somatostatin antisera. In serial sections of pancreatic islets of the man and rabbit, it was shown that amylin immunoreactivity occurred in insulin-reactive B cells predominantly located in interior of the islets. In contrast, amylin immunoreacivity appeared in glucagon-reactive A cells peripherally located in the islets of the guinea pig. These results suggest that in both the man and rabbit, amylin is synthesized by B cells for subsequent co-secretion with insulin, and that in guinea pig, amylin is synthesized by A cells for co-secretion with glucagon. It thus appears that amylin release may be mediated by different secretory mechanisms according to animal species.
Amyloid ; Animals ; B-Lymphocytes ; Glucagon ; Guinea Pigs* ; Guinea* ; Immune Sera ; Immunohistochemistry ; Insulin ; Islet Amyloid Polypeptide* ; Islets of Langerhans* ; Rats ; Somatostatin-Secreting Cells

To explore the possible new mechanism of acupuncture in the treatment of diabetes mellitus type 2 (T2DM) based on the islet inflammatory response. Islet macrophages, pancreatic adipose cells and islet β cells all participate in the pathogenesis of T2DM, and the three could form a network interaction. Acupuncture could regulate the functional phenotype of islet macrophages, improve the ectopic deposition of pancreatic adipose and repair the function of islet β cells, and play a unique advantage of overall regulation. It is suggested that acupuncture can be a potential treatment strategy for T2DM.
Acupuncture Therapy ; Diabetes Mellitus, Type 2/therapy* ; Humans ; Insulin-Secreting Cells/pathology* ; Islets of Langerhans/pathology* ; Macrophages

Insulin is produced and secreted by pancreatic β cells in the pancreas, which plays a key role in maintaining euglycemia. Insufficient secretion or deficient usage of insulin is the main cause of diabetes mellitus (DM). Drug therapy and islets transplantation are classical treatments for DM. Pancreatic β cell replacement therapy could help patients to get rid of drugs and alleviate the problem of lacking in transplantable donors. Pancreatic β-like cells can be acquired by cell reprogramming techniques or directed induction of stem cell differentiation. These cells are proved to be functional both in vitro and in vivo. Some hospitals have already performed clinical trials for pancreatic β cell replacement therapy. Functional pancreatic β-like cells, which obtained from in vitro pathway, could be a reliable source of cell therapy for treating DM. In this review, the approaches of obtaining pancreatic β cells are summarized and the remaining problems are discussed. Some thoughts are provided for further acquisition and application of pancreatic β cells.
Cell Differentiation ; Diabetes Mellitus/therapy* ; Humans ; Insulin/metabolism* ; Insulin-Secreting Cells/metabolism* ; Islets of Langerhans Transplantation ; Pancreas/metabolism*

No abstract available.
Islets of Langerhans* ; Pancreas*

No abstract available.
Islets of Langerhans* ; Pheochromocytoma*

No abstract available.
Hyperplasia* ; Islets of Langerhans* ; Nesidioblastosis*

Humans ; Islets of Langerhans Transplantation

In the conventional treatments of type I diabetes, there are various problems. As a new adequate treatment of diabetes, cell replacement therapy of diabetes has been applied and given research priority. We have investigated the applications of cell transplantation in the treatment of diabetes and have retrieved the relevant articles on cells transplantation for the treatment of diabetes. In this paper, we review the history, development, merits and demerits of cell transplantation and the recent advances in pancreatic islet transplantation research. The latest progress in the induction of stem cell to differentiate into the insulin-producing cells was also introduced.
Animals ; Diabetes Mellitus, Type 1 ; surgery ; therapy ; Humans ; Insulin-Secreting Cells ; cytology ; Islets of Langerhans Transplantation ; methods ; Stem Cell Transplantation

Type 1 diabetes (T1D) is caused by dysregulation of the immune system in the pancreatic islets, which eventually leads to insulin-producing pancreatic beta-cell death and destabilization of glucose homeostasis. One of the major characteristics of T1D pathogenesis is the production of inflammatory mediators by macrophages that result in destruction or damage of pancreatic beta-cells. In this study the inflammatory microenvironment of T1D was simulated with RAW264.7 cells and MIN6 cells, acting as macrophages and pancreatic beta-cells respectably. In this setting, peroxiredoxin-1, an anti-oxidant enzyme was knocked down to observe its functions in the pathogenesis of T1D. RAW264.7 cells were primed with lipopolysaccharide and co-cultured with MIN6 cells while PRX-1 was knocked down in one or both cell types. Our results suggest that hindrance of PRX-1 activity or the deficiency of this enzyme in inflammatory conditions negatively affects pancreatic beta-cell survival. The observed decrease in viability of MIN6 cells seems to be caused by nitric oxide production. Additionally, it seems that PRX-1 affects previously reported protective activity of IL-6 in pancreatic beta cells as well. These results signify new, undiscovered roles for PRX-1 in inflammatory conditions and may contribute toward our understanding of autoimmunity.
Autoimmunity ; Down-Regulation ; Glucose ; Homeostasis ; Immune System ; Insulin-Secreting Cells ; Interleukin-6 ; Islets of Langerhans ; Macrophages ; Nitric Oxide ; Peroxiredoxins