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Improved Outcomes in Islet Isolation and Transplantation by the Use of a Novel Hemoglobin‐based O 2 Carrier
Author(s) -
Avila J. G.,
Wang Y.,
Barbaro B.,
Gangemi A.,
Qi M.,
Kuechle J.,
Doubleday N.,
Doubleday M.,
Churchill T.,
Salehi P.,
Shapiro J.,
Philipson L. H.,
Benedetti E.,
Lakey J. R. T.,
Oberholzer J.
Publication year - 2006
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2006.01551.x
Subject(s) - islet , hemoglobin , medicine , transplantation , oxidative stress , andrology , endocrinology , apoptosis , intracellular , insulin , biochemistry , chemistry
During isolation, islets are exposed to warm ischemia. In this study, intraductal administration of oxygenated polymerized, stroma‐free hemoglobin‐pyridoxalated (Poly SFH‐P) was performed to improve O 2 delivery. Rat pancreata subjected to 30‐min warm ischemia were perfused intraductally with collagenase in oxygenated Poly SFH‐P/RPMI or RPMI (control). PO 2 was increased by Poly SFH‐P (381.7 ± 35.3 mmHg vs. 202.3 ± 28.2, p = 0.01) and pH maintained within physiological range (7.4–7.2 vs. 7.1–6.6, p = 0.009). Islet viability (77%± 4.6 vs. 63%± 4.7, p = 0.04) was improved and apoptosis lower with Poly SFH‐P (caspase‐3: 34,714 ± 2167 vs. 45,985 ± 1382, respectively, p = 0.01). Poly SFH‐P improved islet responsiveness to glucose as determined by increased intracellular Ca 2+ levels and improved insulin secretion (SI 5.4 ± 0.1 vs. 3.1 ± 0.2, p = 0.03). Mitochondrial integrity was improved in Poly SFH‐P‐treated islets, which showed higher percentage change in membrane potential after glucose stimulation (14.7%± 1.8 vs. 9.8 ± 1.4, respectively, p < 0.05). O 2 delivery by Poly SFH‐P did not increase oxidative stress (GSH 7.1 ± 2.9 nm/mg protein for Poly SFH‐P vs. 6.8 ± 2.4 control, p = 0.9) or oxidative injury (MDA 1.8 ± 0.9 nmol/mg protein vs. 6.2 ± 2.4, p = 0.19). Time to reach normoglycemia in transplanted diabetic nude mice was shorter (1.8 ± 0.4 vs. 7 ± 2.5 days, p = 0.02), and glucose tolerance improved in the Poly SFH‐P group (AUC 8106 ± 590 vs. 10,863 ± 946, p = 0.03). Oxygenated Poly SFH‐P improves islet isolation and transplantation outcomes by preserving mitochondrial integrity.