Co‐microencapsulation of human umbilical cord‐derived mesenchymal stem and pancreatic islet‐derived insulin producing cells in experimental type 1 diabetes

Abstract

Introduction Post‐partum umbilical cord Wharton Jelly‐derived adult mesenchymal stem cells (hUCMS) hold anti‐inflammatory and immunosuppressive properties. Human pancreatic islet‐derived progenitor cells (hIDC) may de‐differentiate, and subsequently re‐differentiate into insulin producing cells. The two cell types share common molecules that facilitate their synergistic interaction and possibly crosstalk, likely useful for the cell therapy of type 1 diabetes (T1D). Materials and methods Upon microencapsulation in sodium alginate (AG), hUCMS and hIDC were able to form cell co‐aggregates that looked well integrated and viable. We then grafted microencapsulated hUCMS/hIDC co‐aggregates into non‐obese diabetic/severe combined immunodeficient (NOD/SCID) mice, and observed an acquired ability of cells to produce and store hormones. Finally, we transplanted these biohybrid constructs into NOD mice with recent onset, spontaneous overt diabetes, observing a decline of blood glucose levels. Results In vitro, we have shown that hUCMS inhibited proliferation of allogeneic polymorphonuclear blood cells from patients with T1D, while promoting expansion of FoxP3+ Tregs. Reversal of hyperglycemia in diabetic NODs seems to suggest that hUCMS and hIDC, upon co‐microencapsulation, anatomically and functionally synergized to accomplish two goals: maintain tracer insulin output by hIDC, while exploting the immunoregulatory properties of hUCMS. Conclusion We have gathered preliminary evidence that the two adult stem cell types within AG microcapsules, may synergistically promote tracer insulin production, while “freezing” the autoimmune disease process, and help reversal of the recent onset hyperglycemia in a spontaneous, autoimmune rodent model of diabetes, the NOD mouse, with no need for pharmacologic immunosuppression.

Therapeutic Effects of Insulin-Producing Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Type 1 Diabetes Mouse Model

“…If ISDs are not required following MSC transplantation, the associated medical care costs would be reduced while improving the patient quality of life [58]. It should also be noted that the development of IPC cell therapy requires the encapsulation of islet cells and nanotechnology that can safely deliver them and protect them against immune cells [59][60][61][62].…”

“…IPCs were induced using a modified three-step, 10-day version of the insulin-transferrinselenium (ITS) induction method first established in tonsil MSCs [60,66]. In step 1, hUC-MSCs and hAD-MSCs in high-glucose alpha-minimal essential medium (α-MEM; HyClone Laboratories, Logan, UT, USA) were seeded in an uncoated 90 mm × 15 mm dish (Nunc, Naperville, IL, USA) with bovine serum albumin (BSA; Sigma-Aldrich, St. Louis, MO, USA) without 1% fatty acids (Sigma-Aldrich, St. Louis, MO, USA), and ITS media supplement was added at 37 • C in a 5% CO 2 incubator for 2-day.…”

PDX1−/NKX6.1+ progenitors derived from human pluripotent stem cells as a novel source of insulin‐secreting cells

“…In sum, there is compelling evidence that multiple precursors exist that give rise to insulin‐secreting cells in humans 11–13 and hence can be exploited for cell therapy for diabetes. Recently, it has been found that co‐transplantation of human pancreatic islet‐derived progenitor cells together with MSCs derived from umbilical cord Wharton Jelly in microencapsulated alginate reverses hyperglycaemia in T1D mouse model 14 . These findings suggest the synergetic effect between both cell types in reversing hyperglycaemia of T1D model.…”

An Overview of Engineered Hydrogel-Based Biomaterials for Improved β-Cell Survival and Insulin Secretion

“…The study demonstrated the remarkable role of the ECM-like alginate microcapsule and the co-encapsulation of postpartum umbilical cord Wharton’s Jelly–derived adult MSCs in protecting insulin-producing cells from the host immune system. It also showed that transplantation of human pancreatic islet-derived progenitor cells alone worked within a specific time frame, while the prepared microsystem extended graft function for 180 days ( Montanucci et al, 2020 ).…”