Microwell scaffolds for the extrahepatic transplantation of islets of Langerhans.

Allogeneic islet transplantation into the liver has the potential to restore normoglycemia in patients with type 1 diabetes. However, the suboptimal microenvironment for islets in the liver is likely to be involved in the progressive islet dysfunction that is often observed post-transplantation. Thi...

Full description

Bibliographic Details
Main Authors: Mijke Buitinga, Roman Truckenmüller, Marten A Engelse, Lorenzo Moroni, Hetty W M Ten Hoopen, Clemens A van Blitterswijk, Eelco Jp de Koning, Aart A van Apeldoorn, Marcel Karperien
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3667808?pdf=render
_version_ 1818791279746613248
author Mijke Buitinga
Roman Truckenmüller
Marten A Engelse
Lorenzo Moroni
Hetty W M Ten Hoopen
Clemens A van Blitterswijk
Eelco Jp de Koning
Aart A van Apeldoorn
Marcel Karperien
author_facet Mijke Buitinga
Roman Truckenmüller
Marten A Engelse
Lorenzo Moroni
Hetty W M Ten Hoopen
Clemens A van Blitterswijk
Eelco Jp de Koning
Aart A van Apeldoorn
Marcel Karperien
author_sort Mijke Buitinga
collection DOAJ
description Allogeneic islet transplantation into the liver has the potential to restore normoglycemia in patients with type 1 diabetes. However, the suboptimal microenvironment for islets in the liver is likely to be involved in the progressive islet dysfunction that is often observed post-transplantation. This study validates a novel microwell scaffold platform to be used for the extrahepatic transplantation of islet of Langerhans. Scaffolds were fabricated from either a thin polymer film or an electrospun mesh of poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT) block copolymer (composition: 4000PEOT30PBT70) and were imprinted with microwells, ∼400 µm in diameter and ∼350 µm in depth. The water contact angle and water uptake were 39±2° and 52.1±4.0 wt%, respectively. The glucose flux through electrospun scaffolds was three times higher than for thin film scaffolds, indicating enhanced nutrient diffusion. Human islets cultured in microwell scaffolds for seven days showed insulin release and insulin content comparable to those of free-floating control islets. Islet morphology and insulin and glucagon expression were maintained during culture in the microwell scaffolds. Our results indicate that the microwell scaffold platform prevents islet aggregation by confinement of individual islets in separate microwells, preserves the islet's native rounded morphology, and provides a protective environment without impairing islet functionality, making it a promising platform for use in extrahepatic islet transplantation.
first_indexed 2024-12-18T15:08:50Z
format Article
id doaj.art-5780d1365e654eb4b630dcc82e4c7b35
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-18T15:08:50Z
publishDate 2013-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-5780d1365e654eb4b630dcc82e4c7b352022-12-21T21:03:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6477210.1371/journal.pone.0064772Microwell scaffolds for the extrahepatic transplantation of islets of Langerhans.Mijke BuitingaRoman TruckenmüllerMarten A EngelseLorenzo MoroniHetty W M Ten HoopenClemens A van BlitterswijkEelco Jp de KoningAart A van ApeldoornMarcel KarperienAllogeneic islet transplantation into the liver has the potential to restore normoglycemia in patients with type 1 diabetes. However, the suboptimal microenvironment for islets in the liver is likely to be involved in the progressive islet dysfunction that is often observed post-transplantation. This study validates a novel microwell scaffold platform to be used for the extrahepatic transplantation of islet of Langerhans. Scaffolds were fabricated from either a thin polymer film or an electrospun mesh of poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT) block copolymer (composition: 4000PEOT30PBT70) and were imprinted with microwells, ∼400 µm in diameter and ∼350 µm in depth. The water contact angle and water uptake were 39±2° and 52.1±4.0 wt%, respectively. The glucose flux through electrospun scaffolds was three times higher than for thin film scaffolds, indicating enhanced nutrient diffusion. Human islets cultured in microwell scaffolds for seven days showed insulin release and insulin content comparable to those of free-floating control islets. Islet morphology and insulin and glucagon expression were maintained during culture in the microwell scaffolds. Our results indicate that the microwell scaffold platform prevents islet aggregation by confinement of individual islets in separate microwells, preserves the islet's native rounded morphology, and provides a protective environment without impairing islet functionality, making it a promising platform for use in extrahepatic islet transplantation.http://europepmc.org/articles/PMC3667808?pdf=render
spellingShingle Mijke Buitinga
Roman Truckenmüller
Marten A Engelse
Lorenzo Moroni
Hetty W M Ten Hoopen
Clemens A van Blitterswijk
Eelco Jp de Koning
Aart A van Apeldoorn
Marcel Karperien
Microwell scaffolds for the extrahepatic transplantation of islets of Langerhans.
PLoS ONE
title Microwell scaffolds for the extrahepatic transplantation of islets of Langerhans.
title_full Microwell scaffolds for the extrahepatic transplantation of islets of Langerhans.
title_fullStr Microwell scaffolds for the extrahepatic transplantation of islets of Langerhans.
title_full_unstemmed Microwell scaffolds for the extrahepatic transplantation of islets of Langerhans.
title_short Microwell scaffolds for the extrahepatic transplantation of islets of Langerhans.
title_sort microwell scaffolds for the extrahepatic transplantation of islets of langerhans
url http://europepmc.org/articles/PMC3667808?pdf=render
work_keys_str_mv AT mijkebuitinga microwellscaffoldsfortheextrahepatictransplantationofisletsoflangerhans
AT romantruckenmuller microwellscaffoldsfortheextrahepatictransplantationofisletsoflangerhans
AT martenaengelse microwellscaffoldsfortheextrahepatictransplantationofisletsoflangerhans
AT lorenzomoroni microwellscaffoldsfortheextrahepatictransplantationofisletsoflangerhans
AT hettywmtenhoopen microwellscaffoldsfortheextrahepatictransplantationofisletsoflangerhans
AT clemensavanblitterswijk microwellscaffoldsfortheextrahepatictransplantationofisletsoflangerhans
AT eelcojpdekoning microwellscaffoldsfortheextrahepatictransplantationofisletsoflangerhans
AT aartavanapeldoorn microwellscaffoldsfortheextrahepatictransplantationofisletsoflangerhans
AT marcelkarperien microwellscaffoldsfortheextrahepatictransplantationofisletsoflangerhans