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Co-encapsulation and co-transplantation of mesenchymal stem cells reduces pericapsular fibrosis and improves encapsulated islet survival and function when allografted

Published on Dec 1, 2017in Scientific Reports4.011
· DOI :10.1038/s41598-017-10359-1
Vijayaganapathy Vaithilingam11
Estimated H-index: 11
(CSIRO: Commonwealth Scientific and Industrial Research Organisation),
Margaret D. M. Evans20
Estimated H-index: 20
(CSIRO: Commonwealth Scientific and Industrial Research Organisation)
+ 3 AuthorsBernard E. Tuch27
Estimated H-index: 27
(CSIRO: Commonwealth Scientific and Industrial Research Organisation)
Abstract
Pericapsular fibrotic overgrowth (PFO) is associated with poor survival of encapsulated islets. A strategy to combat PFO is the use of mesenchymal stem cells (MSC). MSC have anti-inflammatory properties and their potential can be enhanced by stimulation with proinflammatory cytokines. This study investigated whether co-encapsulation or co-transplantation of MSC with encapsulated islets would reduce PFO and improve graft survival. Stimulating MSC with a cytokine cocktail of IFN-γ and TNF-α enhanced their immunosuppressive potential by increasing nitric oxide production and secreting higher levels of immunomodulatory cytokines. In vitro, co-encapsulation with MSC did not affect islet viability but significantly enhanced glucose-induced insulin secretion. In vivo, normoglycemia was achieved in 100% mice receiving islets co-encapsulated with stimulated MSC as opposed to 71.4% receiving unstimulated MSC and only 9.1% receiving encapsulated islets alone. Microcapsules retrieved from both unstimulated and stimulated MSC groups had significantly less PFO with improved islet viability and function compared to encapsulated islets alone. Levels of peritoneal immunomodulatory cytokines IL-4, IL-6, IL-10 and G-CSF were significantly higher in MSC co-encapsulated groups. Similar results were obtained when encapsulated islets and MSC were co-transplanted. In summary, co-encapsulation or co-transplantation of MSC with encapsulated islets reduced PFO and improved the functional outcome of allotransplants.
  • References (64)
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References64
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Implanted spheres of a broad variety of material classes significantly abrogate foreign body reactions and fibrosis in rodent and non-human primates when the spheres are larger than 1.5 mm in diameter.
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Insufficient oxygenation can limit the long-term survival of encapsulated islets in subcutaneous tissue. Transplantation of coencapsulated pig islets with adipose or bone marrow mesenchymal stem cells (AMSCs or BM-MSCs, respectively) was investigated with regard to implant vascularization, oxygenation, and diabetes correction in primates. The in vivo impact of MSCs on graft oxygenation and neovascularization was assessed in rats with streptozotocin (STZ)-induced diabetes that were subcutaneously...
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