title: Bioengineering the Endocrine Pancreas: Intraomental Islet Transplantation Within a Biologic Resorbable Scaffold.
abstract: Transplantation of pancreatic islets is a therapeutic option to preserve or restore β-cell function. Our study was aimed at developing a clinically applicable protocol for extrahepatic transplantation of pancreatic islets. The potency of islets implanted onto the omentum, using an in situ-generated adherent, resorbable plasma-thrombin biologic scaffold, was evaluated in diabetic rat and nonhuman primate (NHP) models. Intraomental islet engraftment in the biologic scaffold was confirmed by achievement of improved metabolic function and preservation of islet cytoarchitecture, with reconstitution of rich intrainsular vascular networks in both species. Long-term nonfasting normoglycemia and adequate glucose clearance (tolerance tests) were achieved in both intrahepatic and intraomental sites in rats. Intraomental graft recipients displayed lower levels of serum biomarkers of islet distress (e.g., acute serum insulin) and inflammation (e.g., leptin and α2-macroglobulin). Importantly, low-purity (30:70% endocrine:exocrine) syngeneic rat islet preparations displayed function equivalent to that of pure (>95% endocrine) preparations after intraomental biologic scaffold implantation. Moreover, the biologic scaffold sustained allogeneic islet engraftment in immunosuppressed recipients. Collectively, our feasibility/efficacy data, along with the simplicity of the procedure and the safety of the biologic scaffold components, represented sufficient preclinical testing to proceed to a pilot phase I/II clinical trial.
authors.affiliation: Cell Transplant Center, Diabetes Research Institute, University of Miami, Miami, FL The DeWitt Daughtry Family Department of Surgery, University of Miami, Miami, FL dberman2@med.miami.edu ricordi@miami.edu antonello.pileggi@nih.gov.
authors.forename: Dora M
authors.initials: DM
authors.lastname: Berman
authors.affiliation: Cell Transplant Center, Diabetes Research Institute, University of Miami, Miami, FL.
authors.forename: R Damaris
authors.initials: RD
authors.lastname: Molano
authors.affiliation: Cell Transplant Center, Diabetes Research Institute, University of Miami, Miami, FL.
authors.forename: Carmen
authors.initials: C
authors.lastname: Fotino
authors.affiliation: Cell Transplant Center, Diabetes Research Institute, University of Miami, Miami, FL.
authors.forename: Ulisse
authors.initials: U
authors.lastname: Ulissi
authors.affiliation: Cell Transplant Center, Diabetes Research Institute, University of Miami, Miami, FL.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gimeno
authors.affiliation: Cell Transplant Center, Diabetes Research Institute, University of Miami, Miami, FL Department of Medicine, University of Miami, Miami, FL.
authors.forename: Armando J
authors.initials: AJ
authors.lastname: Mendez
authors.affiliation: Cell Transplant Center, Diabetes Research Institute, University of Miami, Miami, FL The DeWitt Daughtry Family Department of Surgery, University of Miami, Miami, FL.
authors.forename: Norman M
authors.initials: NM
authors.lastname: Kenyon
authors.affiliation: Cell Transplant Center, Diabetes Research Institute, University of Miami, Miami, FL The DeWitt Daughtry Family Department of Surgery, University of Miami, Miami, FL Department of Microbiology and Immunology, University of Miami, Miami, FL Department of Biomedical Engineering, University of Miami, Miami, FL.
authors.forename: Norma S
authors.initials: NS
authors.lastname: Kenyon
authors.affiliation: Department of Pathology, University of Miami, Miami, FL.
authors.forename: David M
authors.initials: DM
authors.lastname: Andrews
authors.affiliation: Cell Transplant Center, Diabetes Research Institute, University of Miami, Miami, FL The DeWitt Daughtry Family Department of Surgery, University of Miami, Miami, FL Department of Medicine, University of Miami, Miami, FL Department of Microbiology and Immunology, University of Miami, Miami, FL Department of Biomedical Engineering, University of Miami, Miami, FL dberman2@med.miami.edu ricordi@miami.edu antonello.pileggi@nih.gov.
authors.forename: Camillo
authors.initials: C
authors.lastname: Ricordi
authors.affiliation: Cell Transplant Center, Diabetes Research Institute, University of Miami, Miami, FL The DeWitt Daughtry Family Department of Surgery, University of Miami, Miami, FL Department of Microbiology and Immunology, University of Miami, Miami, FL Department of Biomedical Engineering, University of Miami, Miami, FL dberman2@med.miami.edu ricordi@miami.edu antonello.pileggi@nih.gov.
authors.forename: Antonello
authors.initials: A
authors.lastname: Pileggi
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects / Q000737:chemistry; D015415:Biomarkers / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D005240:Feasibility Studies; D005260:Female; D006943:Hyperglycemia / Q000517:prevention & control*; D007165:Immunosuppression Therapy / Q000009:adverse effects; D007515:Islets of Langerhans / Q000166:cytology / Q000648:ultrastructure; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects / Q000276:immunology / Q000379:methods* / Q000473:pathology; D008252:Macaca fascicularis; D008297:Male; D008855:Microscopy, Electron, Scanning; D009852:Omentum; D019397:Pancreas, Artificial / Q000009:adverse effects; D010949:Plasma / Q000737:chemistry / Q000378:metabolism; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D011994:Recombinant Proteins / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism; D013499:Surface Properties; D013917:Thrombin / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000009:adverse effects / Q000737:chemistry; D014183:Transplantation, Heterologous / Q000009:adverse effects; D016042:Transplantation, Heterotopic / Q000009:adverse effects; D014185:Transplantation, Isogeneic / Q000009:adverse effects
chemical_list: D001672:Biocompatible Materials; D015415:Biomarkers; D011994:Recombinant Proteins; D013917:Thrombin; C513462:recombinant human thrombin