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Fibroblast growth factor 7 releasing particles enhance islet engraftment and improve metabolic control following islet transplantation in mice with diabetes

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dc.contributor.advisor Forbes, Shareen
dc.contributor.author Alwahsh, Salamah M
dc.contributor.author Qutachi, Omar
dc.contributor.author Starkey Lewis, Philip J.
dc.contributor.author Forbes, Stuart J.
dc.contributor.author Shakesheff, Kevin M.
dc.contributor.author Forbes, Shareen
dc.date.accessioned 2021-05-04T07:59:51Z
dc.date.accessioned 2022-05-22T08:54:25Z
dc.date.available 2021-05-04T07:59:51Z
dc.date.available 2022-05-22T08:54:25Z
dc.date.issued 2021-01-11
dc.identifier.issn https://pubmed.ncbi.nlm.nih.gov/33428803/
dc.identifier.uri http://localhost:8080/xmlui/handle/123456789/8277
dc.description.abstract Transplantation of islets in type 1 diabetes (T1D) is limited by poor islet engraftment into the liver, with two to three donor pancreases required per recipient. We aimed to condition the liver to enhance islet engraftment to improve long-term graft function. Diabetic mice received a non-curative islet transplant (n = 400 islets) via the hepatic portal vein (HPV) with fibroblast growth factor 7-loaded galactosylated poly(DL-lactide-co-glycolic acid) (FGF7-GAL-PLGA) particles; 26-µm diameter particles specifically targeted the liver, promoting hepatocyte proliferation in short-term experiments: in mice receiving 0.1-mg FGF7-GAL-PLGA particles (60-ng FGF7) vs vehicle, cell proliferation was induced specifically in the liver with greater efficacy and specificity than subcutaneous FGF7 (1.25 mg/kg ×2 doses; ~75-µg FGF7). Numbers of engrafted islets and vascularization were greater in liver sections of mice receiving islets and FGF7-GAL-PLGA particles vs mice receiving islets alone, 72 h posttransplant. More mice (six of eight) that received islets and FGF7-GAL-PLGA particles normalized blood glucose concentrations by 30-days posttransplant, versus zero of eight mice receiving islets alone with no evidence of increased proliferation of cells within the liver at this stage and normal liver function tests. This work shows that liver-targeted FGF7-GAL-PLGA particles achieve selective FGF7 delivery to the liver-promoting islet engraftment to help normalize blood glucose levels with a good safety profile. en_US
dc.description.sponsorship Diabetes UK Grant number 13/0004682, UK Regenerative Medicine Platform Grant number: MR/K026666/1, MRC Computational & Chemical Biology of the Stem Cell Niche (Capital grant): MR/ L012766/1, MRC Regenerative Medicine Grant: MR/S03692X/1, Chief Scientist Office ETM/325, Wellcome Trust–University of Edinburgh Institutional Strategic Support Fund, Edinburgh and Lothian’s Health Foundation Award, Wellcome Trust New Investigator Award (100981/Z/13/Z), and Royal Society Funding (RSG\R1\180079). Sobi Pharmaceuticals donated FGF7 under a material transfer agreement for use in subcutaneous injections only in mice in the Diabetes UK funded grant. The University of Nottingham and the University of Edinburgh have a joint UK Patent Application: No. 1818977.9. Date of Filing: November 21, 2018 en_US
dc.publisher Wiley en_US
dc.subject animal models: murine; diabetes: type 1; islet transplantation; regenerative medicine; translational research/science en_US
dc.title Fibroblast growth factor 7 releasing particles enhance islet engraftment and improve metabolic control following islet transplantation in mice with diabetes en_US
dc.type Article en_US

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