Background: MSC exhibit immunomodulatory and anti-inflammatory properties. Notably, MSC were shown to preserve human islet function and to prevent cytokine-induced apoptosis. Aim: To evaluate the effects of human Multipotent Mesenchymal Stromal Cells (MSC) co-encapsulated with human pancreatic islets on islet survival and function. Methods: Human islets or pseudo-islets, obtained after re-aggregation of dispersed islet cells, were co-encapsulated with human bone-marrow derived MSC, in new hydrogel microspheres composed of calcium alginate and covalently cross-linked polyethylene glycol. Encapsulated cells were transplanted intra-peritoneally in streptozotocin-induced diabetic mice. In mice, islet function was followed by measuring glycemia and evaluated by intraperitoneal glucose tolerance test at day 15. Grafts were retrieved after 15 days for morphological analysis. Insulin secretion was tested in vitro by static incubation for islets or pseudo-islets cultured with or without MSC. Results: In diabetic mice, free islets were rejected in 6±1 days (p<0.001), encapsulated islets maintained normoglycemia up to 70 days whilst islets co-encapsulated with MSC prolonged normoglycemia up to 90 days (p<0.05). Further, mice transplanted with encapsulated islets and MSC showed improved glycemic responses compared to mice transplanted with encapsulated islets alone (p<0.001). Graft histological analysis showed MSC to be located within and around the islets (or pseudo-islets). In vitro, insulin secretion was significantly improved when MSC were in cell-cell contact with islets (or pseudo-islets) compared to islets that were only in paracrine exchange with MSC (p<0.05). Conclusions: MSC improve survival and function of human islets in vitro and in vivo. Cell-to-cell contact seems to be necessary to mediate these effects. Whether interactions between adhesion molecules, like cadherins, and/or specific molecules secreted upon contact are involved is currently under investigation.

CITATION INFORMATION: Montanari E, Meier R, Bosco D, Mahou R, Morel P, Seebach J, Wandrey C, Gonelle-Gispert C, Bühler L. Human Multipotent Mesenchymal Stromal Cells Improve Survival and Function of Pancreatic Islets by Cell-to-Cell Contact. Am J Transplant. 2016;16 (suppl 3).

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