A prevascularized subcutaneous device-less site for islet and cellular transplantation

Nat Biotechnol. 2015 May;33(5):518-23. doi: 10.1038/nbt.3211. Epub 2015 Apr 20.

Abstract

Transplantation of donor-derived islets into the liver is a successful cellular replacement therapy for individuals with diabetes. However, the hepatic vasculature is not an optimal transplant site for several reasons, including graft attrition and the inability to retrieve or image the islets. Here we describe islet transplantation into a prevascularized, subcutaneous site created by temporary placement of a medically approved vascular access catheter. In mice with streptozotocin (STZ)-induced diabetes, transplantation of ∼500 syngeneic islets into the resulting 'device-less' space reversed diabetes in 91% of mice and maintained normoglycemia for >100 days. The approach was also effective in mice with pre-existing diabetes, in another mouse strain that mounts a more vigorous inflammatory response, and across an allogeneic barrier. These results demonstrate that transient priming of a subcutaneous site supports diabetes-reversing islet transplantation in mouse models without the need for a permanent cell-encapsulation device.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose
  • Cell- and Tissue-Based Therapy*
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / therapy*
  • Graft Survival
  • Humans
  • Islets of Langerhans Transplantation*
  • Liver
  • Mice
  • Neovascularization, Pathologic / blood
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / therapy*
  • Translational Medical Research

Substances

  • Blood Glucose