Bioengineering the Endocrine Pancreas: Intraomental Islet Transplantation Within a Biologic Resorbable Scaffold

• Published in: Diabetes (New York, N.Y.) Vol. 65; no. 5; pp. 1350 - 1361
• Main Authors: Berman, Dora M, Molano, R Damaris, Fotino, Carmen, Ulissi, Ulisse, Gimeno, Jennifer, Mendez, Armando J, Kenyon, Norman M, Kenyon, Norma S, Andrews, David M, Ricordi, Camillo, Pileggi, Antonello
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.05.2016
• Subjects: Animals; Biocompatible Materials - adverse effects; Biocompatible Materials - chemistry; Bioengineering; Biomarkers - blood; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - immunology; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Experimental - surgery; Endocrine system; Feasibility Studies; Female; Hyperglycemia - prevention & control; Immunology and Transplantation; Immunosuppression Therapy - adverse effects; Islets of Langerhans - cytology; Islets of Langerhans - ultrastructure; Islets of Langerhans Transplantation - adverse effects; Islets of Langerhans Transplantation - immunology; Islets of Langerhans Transplantation - methods; Islets of Langerhans Transplantation - pathology; Macaca fascicularis; Male; Microscopy, Electron, Scanning; Omentum; Pancreas; Pancreas, Artificial - adverse effects; Plasma - chemistry; Plasma - metabolism; Rats, Inbred Lew; Rats, Inbred WF; Recombinant Proteins - adverse effects; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Rodents; Surface Properties; Thrombin - adverse effects; Thrombin - chemistry; Thrombin - metabolism; Tissue Engineering; Tissue Scaffolds - adverse effects; Tissue Scaffolds - chemistry; Transplantation, Heterologous - adverse effects; Transplantation, Heterotopic - adverse effects; Transplantation, Isogeneic - adverse effects; Transplants & implants
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db15-1525

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.