Clinical and Experimental Pancreatic Islet Transplantation to Striated Muscle: Establishment of a Vascular System Similar to that in Native Islets

  1. Mia Phillipson (mia.phillipson{at}mcb.uu.se)1
  1. 1 Department of Medical Cell Biology, Box 571, SE-75123 Uppsala University, Uppsala, Sweden
  2. 2Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden
  3. 3Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden
  4. 4Department for Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
  5. 5Department of Medical Sciences, Uppsala University, Uppsala, Sweden

Abstract

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 which is found applicable to clinical islet transplantation. Islets were implanted into striated muscle where after intra-islet vascular density and blood flow were visualized with intravital and confocal microscopy in mice, and by magnetic resonance imaging in three auto-transplanted 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 to 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 auto-transplanted patients where higher plasma volumes were measured in islets engrafted in forearm muscle compared to 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 intra-islet blood perfusion following transplantation to striated muscle under experimental and clinical situations.

Footnotes