Journal
ISLETS
Volume 8, Issue 6, Pages 186-194Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/19382014.2016.1253652
Keywords
alternative transplant sites; diabetes; human islets; Islet transplantation; murine islets; stem cells; subcutaneous
Categories
Funding
- Diabetes Research Institute Foundation of Canada (DRIFCan)
- Collaborative Research & Innovation Opportunities (CRIO) - Alberta Innovates-Health Solutions (AIHS) [201201154]
- Canadian Institutes of Health Research (CIHR) - Proof of Principle (POP) [144255]
- Senior Clinical Scholarship from Alberta Innovates - Health Solutions (AIHS)
- Canada Research Chair in Transplantation Surgery and Regenerative Medicine through the Government of Canada
- AIHS CRIO Team Award [201201154]
- AIHS Post-Doctoral Fellowship
- AIHS CRIO Team Award
- University of Alberta
- Alberta Diabetes Institute
- Alberta Diabetes Foundation
- Clinician Fellowship from AIHS
- Alberta Innovates [201400496, 201201154] Funding Source: researchfish
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Clinical islet transplantation has routinely been demonstrated to be an efficacious means of restoring glycemic control in select patients with autoimmune diabetes. Notwithstanding marked progress and improvements, the broad-spectrum application of this treatment option is restricted by the complications associated with intrahepatic portal cellular infusion and the scarcity of human donor pancreata. Recent progress in stem cell biology has demonstrated that the potential to expand new cells for clinical transplantation is now a reality. As such, research focus is being directed toward optimizing safe extrahepatic transplant sites to house future alternative cell sources for clinical use. The present study expands on our previous development of a prevascularized subcutaneous device-less (DL) technique for cellular transplantation, by demonstrating long-term (>365d) durable syngeneic murine islet graft function. Furthermore, histological analysis of tissue specimens collected immediately post-DL site creation and acutely post-human islet transplantation demonstrates that this technique results in close apposition of the neovascularized collagen to the transplanted cells without dead space, thereby avoiding hypoxic luminal dead-space. Murine islets transplanted into the DL site created by a larger luminal diameter (6-Fr.) (n = 11), reversed diabetes to the similar capacity as our standard DL method (5-Fr.)(n = 9). Furthermore, glucose tolerance testing did not differ between these 2 transplant groups (p > 0 .05). Taken together, this further refinement of the DL transplant approach facilitates a simplistic means of islet infusion, increases the transplant volume capacity and may provide an effective microenvironment to house future alternative cell sources.
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