Preservation of Human Islet Cell Functional Mass by Anti-Oxidative Action of a Novel SOD Mimic Compound
- Rita Bottino1,
- A.N. Balamurugan12,
- Suzanne Bertera1,
- Massimo Pietropaolo1,
- Massimo Trucco1 and
- Jon D. Piganelli1
- 1Department of Pediatrics, Division of Immunogenetics, Diabetes Institute, University of Pittsburgh, School of Medicine, Rangos Research Center, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania
- 2Department of Surgery, Thomas E. Starlz Transplantation Institute, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania
The most commonly used technical approach to isolate human pancreatic islets intended for allotransplants generates a product that is hampered by mechanical and chemical insults, which dramatically reduce the mass of viable and functional transplantable cells. We tested a novel class of antioxidant chemical compounds (SOD mimics: AEOL10113 and AEOL10150) to protect human islets from oxidative stress in order to improve the preservation of the isolated tissue. Addition of SOD mimic in culture, after isolation, allowed for the survival of a significantly higher islet cell mass. Functional behavior and phenotypic cell characteristics of the SOD-treated islet preparations were preserved, as was the capacity to normalize diabetic mice, even when a marginal mass of islets was transplanted. The addition of SOD mimic during isolation, before culture, further reduced early cell loss. These results indicate that prompt interventions aimed at blocking oxidative stress can improve human islet survival, preserving a functional islet mass two- to threefold larger than the one usually obtained without adding any antioxidant compound. The ability to preserve functional islets without a dramatic loss represents a major advantage considering the scarce availability of islet tissue for clinical transplantation.
Address correspondence and reprint requests to Jon D. Piganelli, PhD, Division of Immunogenetics, Diabetes Institute, Rangos Research Center, Children’s Hospital of Pittsburgh, 3460 Fifth Ave., Pittsburgh, Pennsylvania 15213. E-mail:.
Received for publication 27 March 2002 and accepted in revised form 16 May 2002.
ELISA, enzyme-linked immunosorbent assay; KRBB, Krebs-Ringer bicarbonate buffer.