The metalloporphyrin BMX-010 in human islet isolation and clinical transplantation

CellR4 2016; 4 (3): e2066

  Topic: Islet transplantation     Category:

Abstract

Introduction: Despite the success of islet transplantation, islet loss during isolation and culture remains an enduring obstacle.

Background: Islets are known to have poor defense mechanisms against the accumulation of free radicals. Antioxidants have proven to be beneficial for improving islet viability and function during culture.

This pilot study evaluates the benefits of the metalloporphyrin BMX-010 for clinical islet transplantation.

Materials and Methods: Islets were isolated from 6 human pancreases in the presences of BMX-010 (34 μmol/L) supplementation. Treatment isolations were matched with 14 comparable non-research clinical isolation controls. All islet preparations were assessed for viability and function and subsequently transplanted into patients.

Results: Both groups showed similar yield (BMX: 511,581 IEQ vs. Controls: 395,021 IEQ, p=0.28) and comparable insulin release (stimulation index 4.48 ± 1.8 vs. 3.3 ± 0.7, p=0.45) after a median culture period of 33 hours. Oxygen consumption rate and fractional viability were also similar before transplant (p=0.14 and p=0.68, respectively). Isolations were more likely to be used in transplant when supplemented with BMX-010 (5/6; 83% vs. 8/14; 57%, p=0.26). Post-transplant graft function was also similar for both groups.

Discussion: BMX-010 did not impair human islet function but did not provide detectable benefit to cell yield or transplant efficacy compared to controls. Conversely, pre-clinical studies were encouraging. This may suggest that contrary to prior studies, cell death activation pathways may be less activated in clinical islet transplantation than previously estimated; alternatively, dose delivery or other parameters may be suboptimal.

Conclusions: We demonstrate herein that addition of BMX-010 across the islet isolation process does not affect human islet yield, post culture survival or beta cell function.

To cite this article

The metalloporphyrin BMX-010 in human islet isolation and clinical transplantation

CellR4 2016; 4 (3): e2066

Publication History

Submission date: 02 Apr 2016

Revised on: 14 May 2016

Accepted on: 28 May 2016

Published online: 06 Jun 2016