Mitigating hypoxic stress on pancreatic islets via in situ oxygen generating biomaterial.
A major obstacle in the survival and efficacy of tissue engineered transplants is inadequate oxygenation, whereby unsupportive oxygen tensions result in significant cellular dysfunction and death within the implant. In a previous report, we developed an innovative oxygen generating biomaterial, termed OxySite, to provide supportive in situ oxygenation to cells and prevent hypoxia-induced damage. Herein, we explored the capacity of this biomaterial to mitigate hypoxic stress in both rat and nonhuman primate pancreatic islets by decreasing cell death, supporting metabolic activity, sustaining aerobic metabolism, preserving glucose responsiveness, and decreasing the generation of inflammatory cytokines. Further, the impact of supplemental oxygenation on in vivo cell function was explored by the transplantation of islets previously co-cultured with OxySite into a diabetic rat model. Transplant outcomes revealed significant improvement in graft efficacy for OxySite-treated islets, when transplanted within an extrahepatic site. These results demonstrate the potency of the OxySite material to mitigate activation of detrimental hypoxia-induced pathways in islets during culture and highlights the importance of in situ oxygenation on resulting islet transplant outcomes.
Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA; Diabetes Research Institute, University of Miami, Miami, FL, USA; Department of Biomedical Engineering, University of Miami, Miami, FL, USA.
Maria M
MM
Coronel
Department of Biochemistry and Molecular Biology, University of Miami, Miami, FL, USA.
Ryan
R
Geusz
Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA; Diabetes Research Institute, University of Miami, Miami, FL, USA; Department of Biomedical Engineering, University of Miami, Miami, FL, USA; Department of Biochemistry and Molecular Biology, University of Miami, Miami, FL, USA. Electronic address: cstabler@bme.ufl.edu.
Cherie L
CL
Stabler
D000693:Anaerobiosis; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D018920:Coculture Techniques; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000628:therapy; D006019:Glycolysis / Q000187:drug effects; D000860:Hypoxia / Q000473:pathology*; D007249:Inflammation / Q000473:pathology; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology*; D016381:Islets of Langerhans Transplantation; D008252:Macaca fascicularis; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology*; D011917:Rats, Inbred Lew; D013312:Stress, Physiological / Q000187:drug effects*; D014022:Tissue Survival / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D001672:Biocompatible Materials; D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A; D010100:Oxygen
Beta-cell stress; Biomaterials; Hypoxia; Oxygen