Fibroblast Cell-Based Therapy for Experimental Autoimmune Diabetes

PloS One
Reza B JaliliAziz Ghahary

Abstract

Type 1 diabetes (T1D) results from autoimmune destruction of insulin producing β cells of the pancreatic islets. Curbing autoimmunity at the initiation of T1D can result in recovery of residual β cells and consequently remission of diabetes. Here we report a cell-based therapy for autoimmune diabetes in non-obese diabetic (NOD) mice using dermal fibroblasts. This was achieved by a single injection of fibroblasts, expressing the immunoregulatory molecule indoleamine 2,3 dioxygenase (IDO), into peritoneal cavity of NOD mice shortly after the onset of overt hyperglycemia. Mice were then monitored for reversal of hyperglycemia and changes in inflammatory/regulatory T cell profiles. Blood glucose levels dropped into the normal range in 82% of NOD mice after receiving IDO-expressing fibroblasts while all control mice remained diabetic. We found significantly reduced islet inflammation, increased regulatory T cells, and decreased T helper 17 cells and β cell specific autoreactive CD8+ T cells following IDO cell therapy. We further showed that some of intraperitoneal injected fibroblasts migrated to local lymph nodes and expressed co-inhibitory molecules. These findings suggest that IDO fibroblasts therapy can reinstate self-tolerance ...Continue Reading

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Citations

May 16, 2018·Cell Transplantation·Sanam Salimi ElizeiAziz Ghahary
Feb 15, 2019·Nature Reviews. Drug Discovery·Michael PlattenChristiane A Opitz
Jun 25, 2020·Scientific Reports·Ashley AllenRita N Barcia
Oct 25, 2020·International Journal of Molecular Sciences·Guillaume HarléStéphanie Hugues
Jan 10, 2021·Stem Cell Reviews and Reports·Lacy E LowryJames A Bynum
Feb 8, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Pengcheng LiJia Song
May 27, 2021·The British Journal of Dermatology·S M LwinC E M Griffiths

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Methods Mentioned

BETA
light microscopy
PCR
electrophoresis
lavage
flow cytometry
confocal microscopy

Software Mentioned

Zen

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