Co-Microencapsulation of Islets and MSC CellSaics, Mosaic-Like Aggregates of MSCs and Recombinant Peptide Pieces, and Therapeutic Effects of Their Subcutaneous Transplantation on Diabetes

Abstract

The subcutaneous transplantation of microencapsulated islets has been extensively studied as a therapeutic approach for type I diabetes. However, due to the lower vascular density and strong inflammatory response in the subcutaneous area, there have been few reports of successfully normalized blood glucose levels. To address this issue, we developed mosaic-like aggregates comprised of mesenchymal stem cells (MSCs) and recombinant peptide pieces called MSC CellSaics, which provide a continuous release of angiogenic factors and anti-inflammatory cytokines. Our previous report revealed that the diabetes of immunodeficient diabetic model mice was reversed by the subcutaneous co-transplantation of the MSC CellSaics and rat islets. In this study, we focused on the development of immune-isolating microcapsules to co-encapsulate the MSC CellSaics and rat islets, and their therapeutic efficiency via subcutaneous transplantation into immunocompetent diabetic model mice. As blood glucose level was monitored for 28 days following transplantation, the normalization rate of the new immuno-isolating microcapsules was confirmed to be significantly higher than those of the microcapsules without the MSC CellSaics, and the MSC CellSaics transplanted outside the microcapsules (p < 0.01). Furthermore, the number of islets required for the treatment was reduced. In the stained sections, a larger number/area of blood vessels was observed around the new immuno-isolating microcapsules, which suggests that angiogenic factors secreted by the MSC CellSaics through the microcapsules function locally for their enhanced efficacy.

Stemness maintenance of stem cells derived from human exfoliated deciduous teeth (SHED) in 3D spheroid formation through the TGF-β/Smad signaling pathway

“…Our study showed that 3D spheroid formation significantly increased the secretion and mRNA levels of TGF-β, as well as activated the TGF-β/Smad signaling pathway in SHED. The increased immunomodulatory activity of human MSCs in spheroids may be attributed to enhanced intercellular adhesions and cell contactdependent signaling, which have also been associated with the heightened paracrine activity of MSC aggregates [81,82].…”

3D Bioprinting for Pancreas Engineering/Manufacturing

“…Likewise, mesenchymal stem cells (MSCs) can release soluble cytokines and growth factors to neighboring cells to suppress the immune response, resulting in no local immunosuppression for MS [ 33 ]. In this context, MSCs and islet cells were simultaneously encapsulated into alginate hydrogel to improve the survival rate of the transplanted islet cells, promoting insulin secretion and new blood vessel formation [ 34 , 35 ].…”

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].…”