A New Islet Transplantation Method Combining Mesenchymal Stem Cells with Recombinant Peptide Pieces, Microencapsulated Islets, and Mesh Bags

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.

Advances in Encapsulation and Delivery Strategies for Islet Transplantation

“…The new method improved the efficacy of islet transplantation. [ 129 ] Kerby et al. incorporated mouse islets and kidney MSCs into alginate hydrogels, and transplanted them into diabetic mice.…”

“…[123] Mesenchymal stem cells (MSCs) Alginate microcapsules Improved islet transplantation efficacy. [129] Mesenchymal stem cells (MSCs) Alginate microcapsules Improved the secretion of glucose-stimulated insulin.…”

Tissue Engineering Strategies for Improving Beta Cell Transplantation Outcome

“…Encapsulation of islets together with MSCs or ASCs in hydrogel-based beads has also been demonstrated as a strategy to protect the cells from the host immune system [53][54][55]. Production of growth factors, anti-inflammatory cytokines, and adhesion molecules by MSCs encapsulated with islets has been shown to preserve islet function via increased secretion of anti-oxidant factors and adhesion molecules by islet Fig.…”

The Roles of Collagen in Islet Transplantation

“…They form 100-150 µm-sized pseudoislets with high survival rate and good glucose-stimulated insulin secretion and revealed the improvement of the endocrine function of diabetic animals by transplantation [79]. Recently, Kogawa, Mochizuki, and colleagues showed that the encapsulation technique using human recombinant collagen I (Cellsaic) with mesenchymal stem cells contributed to the improvement of transplant efficacy of islet xenotransplantation by promoting angiogenesis [80,81].…”