title: Improvement of islet engrafts by enhanced angiogenesis and microparticle-mediated oxygenation.
abstract: A major hindrance in islet transplantation as a feasible therapeutic approach for patients with type 1 diabetes is the insufficient oxygenation of the grafts, which results in cell death in portions of the implant. Here we address this limitation through the application of oxygen-generating microparticles (MP) and a fibrin-conjugated heparin/VEGF collagen scaffold to support cell survival by using a β cell line and pancreatic rat islets. MP are composed of a polyvinylpyrrolidone/hydrogen peroxide (PVP/H2O2) core and poly(D,L-lactide-co-glycolide) (PLGA) shell, along with immobilized catalase on the shell. The presence of MP is sufficient to reduce hypoxia-induced cell dysfunction and death for both cell types, resulting in localization of hypoxia-inducible factor (HIF-1α) into the cytoplasm and enhanced metabolic function. After co-transplantation of MP and a reduced islet mass (250 islet equivalents) within an angiogenic scaffold in the omental pouch of streptozotocin-induced diabetic nude mice, we have observed significantly promoted graft function as evidenced by improved blood glucose levels, body weight, glucose tolerance, serum C-peptide, and graft revascularization. These results suggest that the developed platform has great potential to enhance the efficacy for implants in cases where the cell dosage is critical for efficacy, such as islet transplantation and ischemic tissues.
authors.affiliation: Department of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Montazeri
authors.affiliation: Department of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran. Electronic address: semami@aut.ac.ir.
authors.forename: Shahriar
authors.initials: S
authors.lastname: Hojjati-Emami
authors.affiliation: National Cell Bank, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Shahin
authors.initials: S
authors.lastname: Bonakdar
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors.forename: Yaser
authors.initials: Y
authors.lastname: Tahamtani
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors.forename: Ensiyeh
authors.initials: E
authors.lastname: Hajizadeh-Saffar
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors.forename: Marjan
authors.initials: M
authors.lastname: Noori-Keshtkar
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Najar-Asl
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors.forename: Mohammad Kazemi
authors.initials: MK
authors.lastname: Ashtiani
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran. Electronic address: Baharvand@Royaninstitute.org.
authors.forename: Hossein
authors.initials: H
authors.lastname: Baharvand
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002374:Catalase / Q000737:chemistry / Q000378:metabolism*; D015687:Cell Hypoxia; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000628:therapy*; D004800:Enzymes, Immobilized / Q000737:chemistry / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006085:Graft Survival; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D019344:Lactic Acid / Q000737:chemistry; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D010100:Oxygen / Q000008:administration & dosage / Q000378:metabolism*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011205:Povidone / Q000737:chemistry; D051381:Rats; D054457:Tissue Scaffolds / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004800:Enzymes, Immobilized; D042461:Vascular Endothelial Growth Factor A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006861:Hydrogen Peroxide; D002374:Catalase; D011205:Povidone; D010100:Oxygen
keywords: Angiogenesis; Diabetes; Islet transplantation; Oxygen-generating microparticle