Cargando…

Co-Transplantation of Endothelial Progenitor Cells and Pancreatic Islets to Induce Long-Lasting Normoglycemia in Streptozotocin-Treated Diabetic Rats

Graft vascularization is a crucial step to obtain stable normoglycemia in pancreatic islet transplantation. Endothelial progenitor cells (EPCs) contribute to neoangiogenesis and to the revascularization process during ischaemic events and play a key role in the response to pancreatic islet injury. I...

Descripción completa

Detalles Bibliográficos
Autores principales: Quaranta, Paola, Antonini, Sara, Spiga, Saturnino, Mazzanti, Benedetta, Curcio, Michele, Mulas, Giovanna, Diana, Marco, Marzola, Pasquina, Mosca, Franco, Longoni, Biancamaria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3986409/
https://www.ncbi.nlm.nih.gov/pubmed/24733186
http://dx.doi.org/10.1371/journal.pone.0094783
_version_ 1782311705175392256
author Quaranta, Paola
Antonini, Sara
Spiga, Saturnino
Mazzanti, Benedetta
Curcio, Michele
Mulas, Giovanna
Diana, Marco
Marzola, Pasquina
Mosca, Franco
Longoni, Biancamaria
author_facet Quaranta, Paola
Antonini, Sara
Spiga, Saturnino
Mazzanti, Benedetta
Curcio, Michele
Mulas, Giovanna
Diana, Marco
Marzola, Pasquina
Mosca, Franco
Longoni, Biancamaria
author_sort Quaranta, Paola
collection PubMed
description Graft vascularization is a crucial step to obtain stable normoglycemia in pancreatic islet transplantation. Endothelial progenitor cells (EPCs) contribute to neoangiogenesis and to the revascularization process during ischaemic events and play a key role in the response to pancreatic islet injury. In this work we co-transplanted EPCs and islets in the portal vein of chemically-induced diabetic rats to restore islet vascularization and to improve graft survival. Syngenic islets were transplanted, either alone or with EPCs derived from green fluorescent protein (GFP) transgenic rats, into the portal vein of streptozotocin-induced diabetic rats. Blood glucose levels were monitored and intraperitoneal glucose tolerance tests were performed. Real time-PCR was carried out to evaluate the gene expression of angiogenic factors. Diabetic-induced rats showed long-lasting (6 months) normoglycemia upon co-transplantation of syngenic islets and EPCs. After 3–5 days from transplantation, hyperglycaemic levels dropped to normal values and lasted unmodified as long as they were checked. Further, glucose tolerance tests revealed the animals' ability to produce insulin on-demand as indexed by a prompt response in blood glucose clearance. Graft neovascularization was evaluated by immunohistochemistry: for the first time the measure of endothelial thickness revealed a donor-EPC-related neovascularization supporting viable islets up to six months after transplant. Our results highlight the importance of a newly formed viable vascular network together with pancreatic islets to provide de novo adequate supply in order to obtain enduring normoglycemia and prevent diabetes-related long-term health hazards.
format Online
Article
Text
id pubmed-3986409
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-39864092014-04-15 Co-Transplantation of Endothelial Progenitor Cells and Pancreatic Islets to Induce Long-Lasting Normoglycemia in Streptozotocin-Treated Diabetic Rats Quaranta, Paola Antonini, Sara Spiga, Saturnino Mazzanti, Benedetta Curcio, Michele Mulas, Giovanna Diana, Marco Marzola, Pasquina Mosca, Franco Longoni, Biancamaria PLoS One Research Article Graft vascularization is a crucial step to obtain stable normoglycemia in pancreatic islet transplantation. Endothelial progenitor cells (EPCs) contribute to neoangiogenesis and to the revascularization process during ischaemic events and play a key role in the response to pancreatic islet injury. In this work we co-transplanted EPCs and islets in the portal vein of chemically-induced diabetic rats to restore islet vascularization and to improve graft survival. Syngenic islets were transplanted, either alone or with EPCs derived from green fluorescent protein (GFP) transgenic rats, into the portal vein of streptozotocin-induced diabetic rats. Blood glucose levels were monitored and intraperitoneal glucose tolerance tests were performed. Real time-PCR was carried out to evaluate the gene expression of angiogenic factors. Diabetic-induced rats showed long-lasting (6 months) normoglycemia upon co-transplantation of syngenic islets and EPCs. After 3–5 days from transplantation, hyperglycaemic levels dropped to normal values and lasted unmodified as long as they were checked. Further, glucose tolerance tests revealed the animals' ability to produce insulin on-demand as indexed by a prompt response in blood glucose clearance. Graft neovascularization was evaluated by immunohistochemistry: for the first time the measure of endothelial thickness revealed a donor-EPC-related neovascularization supporting viable islets up to six months after transplant. Our results highlight the importance of a newly formed viable vascular network together with pancreatic islets to provide de novo adequate supply in order to obtain enduring normoglycemia and prevent diabetes-related long-term health hazards. Public Library of Science 2014-04-14 /pmc/articles/PMC3986409/ /pubmed/24733186 http://dx.doi.org/10.1371/journal.pone.0094783 Text en © 2014 Quaranta et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Quaranta, Paola
Antonini, Sara
Spiga, Saturnino
Mazzanti, Benedetta
Curcio, Michele
Mulas, Giovanna
Diana, Marco
Marzola, Pasquina
Mosca, Franco
Longoni, Biancamaria
Co-Transplantation of Endothelial Progenitor Cells and Pancreatic Islets to Induce Long-Lasting Normoglycemia in Streptozotocin-Treated Diabetic Rats
title Co-Transplantation of Endothelial Progenitor Cells and Pancreatic Islets to Induce Long-Lasting Normoglycemia in Streptozotocin-Treated Diabetic Rats
title_full Co-Transplantation of Endothelial Progenitor Cells and Pancreatic Islets to Induce Long-Lasting Normoglycemia in Streptozotocin-Treated Diabetic Rats
title_fullStr Co-Transplantation of Endothelial Progenitor Cells and Pancreatic Islets to Induce Long-Lasting Normoglycemia in Streptozotocin-Treated Diabetic Rats
title_full_unstemmed Co-Transplantation of Endothelial Progenitor Cells and Pancreatic Islets to Induce Long-Lasting Normoglycemia in Streptozotocin-Treated Diabetic Rats
title_short Co-Transplantation of Endothelial Progenitor Cells and Pancreatic Islets to Induce Long-Lasting Normoglycemia in Streptozotocin-Treated Diabetic Rats
title_sort co-transplantation of endothelial progenitor cells and pancreatic islets to induce long-lasting normoglycemia in streptozotocin-treated diabetic rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3986409/
https://www.ncbi.nlm.nih.gov/pubmed/24733186
http://dx.doi.org/10.1371/journal.pone.0094783
work_keys_str_mv AT quarantapaola cotransplantationofendothelialprogenitorcellsandpancreaticisletstoinducelonglastingnormoglycemiainstreptozotocintreateddiabeticrats
AT antoninisara cotransplantationofendothelialprogenitorcellsandpancreaticisletstoinducelonglastingnormoglycemiainstreptozotocintreateddiabeticrats
AT spigasaturnino cotransplantationofendothelialprogenitorcellsandpancreaticisletstoinducelonglastingnormoglycemiainstreptozotocintreateddiabeticrats
AT mazzantibenedetta cotransplantationofendothelialprogenitorcellsandpancreaticisletstoinducelonglastingnormoglycemiainstreptozotocintreateddiabeticrats
AT curciomichele cotransplantationofendothelialprogenitorcellsandpancreaticisletstoinducelonglastingnormoglycemiainstreptozotocintreateddiabeticrats
AT mulasgiovanna cotransplantationofendothelialprogenitorcellsandpancreaticisletstoinducelonglastingnormoglycemiainstreptozotocintreateddiabeticrats
AT dianamarco cotransplantationofendothelialprogenitorcellsandpancreaticisletstoinducelonglastingnormoglycemiainstreptozotocintreateddiabeticrats
AT marzolapasquina cotransplantationofendothelialprogenitorcellsandpancreaticisletstoinducelonglastingnormoglycemiainstreptozotocintreateddiabeticrats
AT moscafranco cotransplantationofendothelialprogenitorcellsandpancreaticisletstoinducelonglastingnormoglycemiainstreptozotocintreateddiabeticrats
AT longonibiancamaria cotransplantationofendothelialprogenitorcellsandpancreaticisletstoinducelonglastingnormoglycemiainstreptozotocintreateddiabeticrats