Clinical and Experimental Pancreatic Islet Transplantation to Striated Muscle
Establishment of a Vascular System Similar to That in Native Islets
- Gustaf Christoffersson1,
- Johanna Henriksnäs1,
- Lars Johansson2,
- Charlotte Rolny3,
- Håkan Ahlström2,
- José Caballero-Corbalan2,
- Ralf Segersvärd4,
- Johan Permert4,
- Olle Korsgren2,
- Per-Ola Carlsson1,5 and
- Mia Phillipson1
- 1Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden;
- 2Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden;
- 3Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden;
- 4Department for Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden;
- 5Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
- Corresponding author: Mia Phillipson, .
OBJECTIVE Curing type 1 diabetes by transplanting pancreatic islets into the liver is associated with poor long-term outcome and graft failure at least partly due to inadequate graft revascularization. The aim of the current study was to evaluate striated muscle as a potential angiogenic site for islet transplantation.
RESEARCH DESIGN AND METHODS The current study presents a new experimental model that is found to be applicable to clinical islet transplantation. Islets were implanted into striated muscle and intraislet vascular density and blood flow were visualized with intravital and confocal microscopy in mice and by magnetic resonance imaging in three autotransplanted pancreatectomized patients. Mice were rendered neutropenic by repeated injections of Gr-1 antibody, and diabetes was induced by alloxan treatment.
RESULTS Contrary to liver-engrafted islets, islets transplanted to mouse muscle were revascularized with vessel densities and blood flow entirely comparable with those of islets within intact pancreas. Initiation of islet revascularization at the muscular site was dependent on neutrophils, and the function of islets transplanted to muscle was proven by curing diabetic mice. The experimental data were confirmed in autotransplanted patients where higher plasma volumes were measured in islets engrafted in forearm muscle compared with adjacent muscle tissue through high-resolution magnetic resonance imaging.
CONCLUSIONS This study presents a novel paradigm in islet transplantation whereby recruited neutrophils are crucial for the functionally restored intraislet blood perfusion following transplantation to striated muscle under experimental and clinical situations.
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- Received February 10, 2010.
- Accepted July 8, 2010.
- © 2010 by the American Diabetes Association.
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