title: Preservation of human islet cell functional mass by anti-oxidative action of a novel SOD mimic compound.
abstract: 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.
authors.affiliation: Department of Pediatrics, Division of Immunogenetics, Diabetes Institute, University of Pittsburgh, School of Medicine, Rangos Research Center, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Bottino
authors.forename: A N
authors.initials: AN
authors.lastname: Balamurugan
authors.forename: Suzanne
authors.initials: S
authors.lastname: Bertera
authors.forename: Massimo
authors.initials: M
authors.lastname: Pietropaolo
authors.forename: Massimo
authors.initials: M
authors.lastname: Trucco
authors.forename: Jon D
authors.initials: JD
authors.lastname: Piganelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology*; D008875:Middle Aged; D009924:Organ Culture Techniques / Q000379:methods; D009926:Organ Preservation / Q000379:methods*; D013997:Time Factors; D014019:Tissue Donors
chemical_list: D000975:Antioxidants; D007328:Insulin; D008665:Metalloporphyrins; C431023:manganese (III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin