BMX-001, a novel redox-active metalloporphyrin, improves islet function and engraftment in a murine transplant model

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
Antonio BruniA M J Shapiro

Abstract

Islet transplantation has become a well-established therapy for select patients with type 1 diabetes. Viability and engraftment can be compromised by the generation of oxidative stress encountered during isolation and culture. We evaluated whether the administration of BMX-001 (MnTnBuOE-2-PyP5+ [Mn(III) meso-tetrakis-(N-b-butoxyethylpyridinium-2-yl)porphyrin]) and its earlier derivative, BMX-010 (MnTE-2-PyP [Mn(III) meso-tetrakis-(N-methylpyridinium-2-yl)porphyrin]) could improve islet function and engraftment outcomes. Long-term culture of human islets with BMX-001, but not BMX-010, exhibited preserved in vitro viability. Murine islets isolated and cultured for 24 hours with 34 μmol/L BMX-001 exhibited improved insulin secretion (n = 3 isolations, P < .05) in response to glucose relative to control islets. In addition, 34 μmol/L BMX-001-supplemented murine islets exhibited significantly reduced apoptosis as indicated by terminal deoxynucleotidyl transferase dUTP nick end labeling, compared with nontreated control islets (P < .05). Murine syngeneic islets transplanted under the kidney capsule at a marginal dose of 150 islets revealed 58% of 34 μmol/L BMX-001-treated islet recipients became euglycemic (n = 11 of 19) compared wit...Continue Reading

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Citations

Sep 25, 2018·Current Opinion in Organ Transplantation·Elisabeth Kemter, Eckhard Wolf
May 28, 2019·Redox Biology·Ines Batinic-Haberle, Margaret E Tome
May 31, 2018·Current Opinion in Organ Transplantation·Andrew R PepperA M James Shapiro
Feb 13, 2021·Cells·Kevin VerhoeffAndrew Mark James Shapiro

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