Abstract | BACKGROUND: METHODS: Two hundred islets were transplanted with or without different doses of PolyHb intramuscularly to nondiabetic C57BL/6 and diabetic C57BL/6 nu/nu mice. β-cell hypoxia and apoptosis were evaluated by immunohistochemistry after injection of the biochemical marker pimonidazole or by staining for caspase-3, respectively. Blood glucose concentrations were monitored for 30 days after islet transplantation and animals were then subjected to an intravenous glucose tolerance test. RESULTS: Substantial hypoxia was observed in control islet grafts during the first 4 days after transplantation. Cotransplantation of PolyHb resulted in a dose-dependent reduction of β-cell hypoxia, but β-cell apoptosis was only reduced by cotransplantation of low-dose PolyHb (0.03 mg/g body weight) due to the inflammatory effects of higher PolyHb concentrations. Cotransplantation of low-dose PolyHb resulted in improved islet graft function 30 days after transplantation in diabetic mice, with a glucose tolerance comparable to transplantation of 50% more islets. CONCLUSION: We conclude that cotransplantation of islets with PolyHb can be used to effectively bridge the critical hypoxic phase immediately after transplantation, improve islet graft function, and reduce the number of islets needed for successful intramuscular transplantation.
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Authors | Daniel Espes, Joey Lau, My Quach, Uddyalok Banerjee, Andre F Palmer, Per-Ola Carlsson |
Journal | Transplantation
(Transplantation)
Vol. 99
Issue 10
Pg. 2077-82
(Oct 2015)
ISSN: 1534-6080 [Electronic] United States |
PMID | 26426924
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Blood Glucose
- Hemoglobins
- Insulin
- Polymers
- polymerized bovine hemoglobin
- Casp3 protein, mouse
- Caspase 3
- Oxygen
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Topics |
- Animals
- Apoptosis
- Blood Glucose
(chemistry)
- Caspase 3
(metabolism)
- Cattle
- Cell Survival
- Glucose Tolerance Test
- Hemoglobins
(chemistry)
- Hypoxia
(pathology)
- Immunohistochemistry
- Injections, Intramuscular
- Insulin
(metabolism)
- Insulin-Secreting Cells
(cytology)
- Islets of Langerhans
(cytology)
- Islets of Langerhans Transplantation
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Nude
- Muscles
(pathology)
- Oxygen
(chemistry)
- Polymers
(chemistry)
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