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

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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384628/
https://www.ncbi.nlm.nih.gov/pubmed/26916086
http://dx.doi.org/10.2337/db15-1525
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author 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
author_facet 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
author_sort Berman, Dora M.
collection PubMed
description 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.
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spelling pubmed-53846282017-05-01 Bioengineering the Endocrine Pancreas: Intraomental Islet Transplantation Within a Biologic Resorbable Scaffold 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 Diabetes Immunology and Transplantation 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. American Diabetes Association 2016-05 2016-02-25 /pmc/articles/PMC5384628/ /pubmed/26916086 http://dx.doi.org/10.2337/db15-1525 Text en © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
spellingShingle Immunology and Transplantation
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
Bioengineering the Endocrine Pancreas: Intraomental Islet Transplantation Within a Biologic Resorbable Scaffold
title Bioengineering the Endocrine Pancreas: Intraomental Islet Transplantation Within a Biologic Resorbable Scaffold
title_full Bioengineering the Endocrine Pancreas: Intraomental Islet Transplantation Within a Biologic Resorbable Scaffold
title_fullStr Bioengineering the Endocrine Pancreas: Intraomental Islet Transplantation Within a Biologic Resorbable Scaffold
title_full_unstemmed Bioengineering the Endocrine Pancreas: Intraomental Islet Transplantation Within a Biologic Resorbable Scaffold
title_short Bioengineering the Endocrine Pancreas: Intraomental Islet Transplantation Within a Biologic Resorbable Scaffold
title_sort bioengineering the endocrine pancreas: intraomental islet transplantation within a biologic resorbable scaffold
topic Immunology and Transplantation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384628/
https://www.ncbi.nlm.nih.gov/pubmed/26916086
http://dx.doi.org/10.2337/db15-1525
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