Journal
DIABETES-METABOLISM RESEARCH AND REVIEWS
Volume 37, Issue 2, Pages -Publisher
WILEY
DOI: 10.1002/dmrr.3372
Keywords
hyperglycemia; insulin; microcapsules; NOD; stem cells; therapy
Categories
Funding
- Altucell Inc., New York, NY (USA) [11746]
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The study found that hUCMS inhibited proliferation of allogeneic polymorphonuclear blood cells from patients with T1D, while promoting expansion of FoxP3(+)Tregs. Through co-microencapsulation, hUCMS and hIDC synergized anatomically and functionally, maintaining tracer insulin output by hIDC and utilizing the immunoregulatory properties of hUCMS to help decrease blood glucose levels.
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.
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