title: A prevascularized subcutaneous device-less site for islet and cellular transplantation.
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.
authors.affiliation: Clinical Islet Transplant Program, Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Pepper
authors.affiliation: Clinical Islet Transplant Program, Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Boris
authors.initials: B
authors.lastname: Gala-Lopez
authors.affiliation: Clinical Islet Transplant Program, Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Rena
authors.initials: R
authors.lastname: Pawlick
authors.affiliation: Clinical Islet Transplant Program, Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Shaheed
authors.initials: S
authors.lastname: Merani
authors.affiliation: 1] Clinical Islet Transplant Program, Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada. [2] Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Tatsuya
authors.identifier: 0000000251796067
authors.initials: T
authors.lastname: Kin
authors.affiliation: 1] Clinical Islet Transplant Program, Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada. [2] Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: A M James
authors.initials: AM
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D001786:Blood Glucose; D064987:Cell- and Tissue-Based Therapy; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000628:therapy*; D006085:Graft Survival; D006801:Humans; D016381:Islets of Langerhans Transplantation; D008099:Liver; D051379:Mice; D009389:Neovascularization, Pathologic / Q000097:blood / Q000473:pathology / Q000628:therapy*; D057170:Translational Research, Biomedical
chemical_list: D001786:Blood Glucose