Improved outcomes in islet isolation and transplantation by the use of a novel hemoglobin-based O2 carrier

被引:28
作者
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. [1 ]
机构
[1] Univ Illinois, Div Transplantat, Chicago, IL 60680 USA
[2] Northfield Labs, Evanston, IL USA
[3] Univ Alberta, Surg Med Res Inst, Edmonton, AB, Canada
[4] Univ Chicago, Dept Med, Chicago, IL 60637 USA
关键词
hemoglobin-based O-2 carriers; islet isolation; islet transplantation;
D O I
10.1111/j.1600-6143.2006.01551.x
中图分类号
R61 [外科手术学];
学科分类号
摘要
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). PO2 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 Ca2+ 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.
引用
收藏
页码:2861 / 2870
页数:10
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