Co-Microencapsulation of human umbilical cord-derived mesenchymal stem and pancreatic islet-derived insulin producing cells: a new experimental approach for the cell therapy of Type 1 Diabetes Mellitus (T1D).

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 T1D. MATERIALS AND METHODS upon microencapsulation in sodium alginate, 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 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 had shown that hUCMS inhibited proliferation of allogeneic polymorphonuclear blood cells (PBMC) from patients with type 1 diabetes, 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 alginate 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. This article is protected by copyright. All rights reserved.