Abstract
Microencapsulated islet transplantation was widely studied as a promising treatment for type 1 diabetes mellitus. However, micro-encapsulated islet transplantation has the following problems—early dysfunction of the islets due to the inflammatory reaction at the transplantation site, and hyponutrition and hypoxia due to a lack of blood vessels around the transplantation site, and difficulty in removal of the islets. On the other hand, we proposed a cell transplantation technique called CellSaic, which was reported to enhance the vascular induction effect of mesenchymal stem cells (MSCs) in CellSaic form, and to enhance the effect of islet transplantation through co-transplantation. Therefore, we performed islet transplantation in diabetic mice by combining three components—microencapsulated islets, MSC-CellSaic, and a mesh bag that encapsulates them and enables their removal. Mesh pockets were implanted in the peritoneal cavity of Balb/c mice as implantation sites. After 4 weeks of implantation, a pocket was opened and transplanted with (1) pancreatic islets, (2) microencapsulated islets, and (3) microencapsulated islets + MSC-CellSaic. Four weeks of observation of blood glucose levels showed that the MSC-CellSaic co-transplant group showed a marked decrease in blood glucose levels, compared to the other groups. A three-component configuration of microcapsules, MSC-CellSaic, and mesh bag was shown to enhance the efficacy of islet transplantation.
Highlights
Diabetes is characterized by chronic hyperglycemia caused by abnormalities in insulin secretion, action, or both
We reported that co-transplantation of mesenchymal stem cells (MSCs)-CellSaic with islets is even more effective than co-transplanting MSC with islets [11]
MSC-Spheroid or MSC-CellSaic was enclosed in bags made of polysulfone membranes that did not pass through the cells, and were implanted subcutaneously in mice
Summary
Diabetes is characterized by chronic hyperglycemia caused by abnormalities in insulin secretion, action, or both. These include destruction by autoimmunity, allogeneic, or xenobiological rejection, limited supply and suboptimal yields of islet procurement and isolation, hypotrophy and hypoxia of transplanted islets, and exposure to the toxic effects of immunosuppressive agents [2]. These are thought to contribute to early graft failure [3]. MSC-CellSaic could be an approach to solve problems such as vascular deficiency around microencapsulated pancreatic islets and rejection caused by inflammation. We investigated the combination of MSC-CellSaic, encapsulated islets and macro pockets in the hope that the problem of encapsulated pancreatic islets could be solved
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