Macroporous three-dimensional PDMS scaffolds for Extrahepatic Islet Transplantation

Eileen Pedraza, Ann Christina Brady, Christopher Fraker, Ruth Molano, Steven Sukert, Dora Berman-Weinberg, Norma S Kenyon, Antonello Pileggi, Camillo Ricordi, Cherie L. Stabler

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Clinical islet transplantation has demonstrated success in treating type 1 diabetes. A current limitation is the intrahepatic portal vein transplant site, which is prone to mechanical stress and inflammation. Transplantation of pancreatic islets into alternative sites is preferable, but challenging, as it may require a three-dimensional vehicle to confer mechanical protection and to confine islets to a well-defined, retrievable space where islet neovascularization can occur. We have fabricated biostable, macroporous scaffolds from poly(dimethylsiloxane) (PDMS) and investigated islet retention and distribution, metabolic function, and glucose-dependent insulin secretion within these scaffolds. Islets from multiple sources, including rodents, nonhuman primates, and humans, were tested in vitro. We observed high islet retention and distribution within PDMS scaffolds, with retention of small islets (<100 μm) improved through the postloading addition of fibrin gel. Islets loaded within PDMS scaffolds exhibited viability and function comparable to standard culture conditions when incubated under normal oxygen tensions, but displayed improved viability compared to standard two-dimensional culture controls under low oxygen tensions. In vivo efficacy of scaffolds to support islet grafts was evaluated after transplantation in the omental pouch of chemically induced diabetic syngeneic rats, which promptly achieved normoglycemia. Collectively, these results are promising in that they indicate the potential for transplanting islets into a clinically relevant, extrahepatic site that provides spatial distribution of islets as well as intradevice vascularization.

Original languageEnglish
Pages (from-to)1123-1125
Number of pages3
JournalCell Transplantation
Volume22
Issue number7
DOIs
StatePublished - Jul 5 2013

Fingerprint

Islets of Langerhans Transplantation
Polydimethylsiloxane
Scaffolds
Oxygen
Transplants
Mechanical Stress
Portal Vein
Fibrin
Type 1 Diabetes Mellitus
Primates
Rodentia
Transplantation (surgical)
Transplantation
Gels
Insulin
Inflammation
Glucose
Medical problems
Grafts
Spatial distribution

Keywords

  • Diabetes
  • Extrahepatic sites
  • Human islets
  • Islet transplantation
  • Nonhuman primate islets
  • Omentum
  • Poly(dimethylsiloxane) (PDMS)
  • Rat islets
  • Scaffold

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

Cite this

Macroporous three-dimensional PDMS scaffolds for Extrahepatic Islet Transplantation. / Pedraza, Eileen; Brady, Ann Christina; Fraker, Christopher; Molano, Ruth; Sukert, Steven; Berman-Weinberg, Dora; Kenyon, Norma S; Pileggi, Antonello; Ricordi, Camillo; Stabler, Cherie L.

In: Cell Transplantation, Vol. 22, No. 7, 05.07.2013, p. 1123-1125.

Research output: Contribution to journalArticle

Pedraza, Eileen ; Brady, Ann Christina ; Fraker, Christopher ; Molano, Ruth ; Sukert, Steven ; Berman-Weinberg, Dora ; Kenyon, Norma S ; Pileggi, Antonello ; Ricordi, Camillo ; Stabler, Cherie L. / Macroporous three-dimensional PDMS scaffolds for Extrahepatic Islet Transplantation. In: Cell Transplantation. 2013 ; Vol. 22, No. 7. pp. 1123-1125.
@article{0d13b04acde1441b835b9259ea4014d4,
title = "Macroporous three-dimensional PDMS scaffolds for Extrahepatic Islet Transplantation",
abstract = "Clinical islet transplantation has demonstrated success in treating type 1 diabetes. A current limitation is the intrahepatic portal vein transplant site, which is prone to mechanical stress and inflammation. Transplantation of pancreatic islets into alternative sites is preferable, but challenging, as it may require a three-dimensional vehicle to confer mechanical protection and to confine islets to a well-defined, retrievable space where islet neovascularization can occur. We have fabricated biostable, macroporous scaffolds from poly(dimethylsiloxane) (PDMS) and investigated islet retention and distribution, metabolic function, and glucose-dependent insulin secretion within these scaffolds. Islets from multiple sources, including rodents, nonhuman primates, and humans, were tested in vitro. We observed high islet retention and distribution within PDMS scaffolds, with retention of small islets (<100 μm) improved through the postloading addition of fibrin gel. Islets loaded within PDMS scaffolds exhibited viability and function comparable to standard culture conditions when incubated under normal oxygen tensions, but displayed improved viability compared to standard two-dimensional culture controls under low oxygen tensions. In vivo efficacy of scaffolds to support islet grafts was evaluated after transplantation in the omental pouch of chemically induced diabetic syngeneic rats, which promptly achieved normoglycemia. Collectively, these results are promising in that they indicate the potential for transplanting islets into a clinically relevant, extrahepatic site that provides spatial distribution of islets as well as intradevice vascularization.",
keywords = "Diabetes, Extrahepatic sites, Human islets, Islet transplantation, Nonhuman primate islets, Omentum, Poly(dimethylsiloxane) (PDMS), Rat islets, Scaffold",
author = "Eileen Pedraza and Brady, {Ann Christina} and Christopher Fraker and Ruth Molano and Steven Sukert and Dora Berman-Weinberg and Kenyon, {Norma S} and Antonello Pileggi and Camillo Ricordi and Stabler, {Cherie L.}",
year = "2013",
month = "7",
day = "5",
doi = "10.3727/096368912X657440",
language = "English",
volume = "22",
pages = "1123--1125",
journal = "Cell Transplantation",
issn = "0963-6897",
publisher = "Cognizant Communication Corporation",
number = "7",

}

TY - JOUR

T1 - Macroporous three-dimensional PDMS scaffolds for Extrahepatic Islet Transplantation

AU - Pedraza, Eileen

AU - Brady, Ann Christina

AU - Fraker, Christopher

AU - Molano, Ruth

AU - Sukert, Steven

AU - Berman-Weinberg, Dora

AU - Kenyon, Norma S

AU - Pileggi, Antonello

AU - Ricordi, Camillo

AU - Stabler, Cherie L.

PY - 2013/7/5

Y1 - 2013/7/5

N2 - Clinical islet transplantation has demonstrated success in treating type 1 diabetes. A current limitation is the intrahepatic portal vein transplant site, which is prone to mechanical stress and inflammation. Transplantation of pancreatic islets into alternative sites is preferable, but challenging, as it may require a three-dimensional vehicle to confer mechanical protection and to confine islets to a well-defined, retrievable space where islet neovascularization can occur. We have fabricated biostable, macroporous scaffolds from poly(dimethylsiloxane) (PDMS) and investigated islet retention and distribution, metabolic function, and glucose-dependent insulin secretion within these scaffolds. Islets from multiple sources, including rodents, nonhuman primates, and humans, were tested in vitro. We observed high islet retention and distribution within PDMS scaffolds, with retention of small islets (<100 μm) improved through the postloading addition of fibrin gel. Islets loaded within PDMS scaffolds exhibited viability and function comparable to standard culture conditions when incubated under normal oxygen tensions, but displayed improved viability compared to standard two-dimensional culture controls under low oxygen tensions. In vivo efficacy of scaffolds to support islet grafts was evaluated after transplantation in the omental pouch of chemically induced diabetic syngeneic rats, which promptly achieved normoglycemia. Collectively, these results are promising in that they indicate the potential for transplanting islets into a clinically relevant, extrahepatic site that provides spatial distribution of islets as well as intradevice vascularization.

AB - Clinical islet transplantation has demonstrated success in treating type 1 diabetes. A current limitation is the intrahepatic portal vein transplant site, which is prone to mechanical stress and inflammation. Transplantation of pancreatic islets into alternative sites is preferable, but challenging, as it may require a three-dimensional vehicle to confer mechanical protection and to confine islets to a well-defined, retrievable space where islet neovascularization can occur. We have fabricated biostable, macroporous scaffolds from poly(dimethylsiloxane) (PDMS) and investigated islet retention and distribution, metabolic function, and glucose-dependent insulin secretion within these scaffolds. Islets from multiple sources, including rodents, nonhuman primates, and humans, were tested in vitro. We observed high islet retention and distribution within PDMS scaffolds, with retention of small islets (<100 μm) improved through the postloading addition of fibrin gel. Islets loaded within PDMS scaffolds exhibited viability and function comparable to standard culture conditions when incubated under normal oxygen tensions, but displayed improved viability compared to standard two-dimensional culture controls under low oxygen tensions. In vivo efficacy of scaffolds to support islet grafts was evaluated after transplantation in the omental pouch of chemically induced diabetic syngeneic rats, which promptly achieved normoglycemia. Collectively, these results are promising in that they indicate the potential for transplanting islets into a clinically relevant, extrahepatic site that provides spatial distribution of islets as well as intradevice vascularization.

KW - Diabetes

KW - Extrahepatic sites

KW - Human islets

KW - Islet transplantation

KW - Nonhuman primate islets

KW - Omentum

KW - Poly(dimethylsiloxane) (PDMS)

KW - Rat islets

KW - Scaffold

UR - http://www.scopus.com/inward/record.url?scp=84879562092&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879562092&partnerID=8YFLogxK

U2 - 10.3727/096368912X657440

DO - 10.3727/096368912X657440

M3 - Article

C2 - 23031502

AN - SCOPUS:84879562092

VL - 22

SP - 1123

EP - 1125

JO - Cell Transplantation

JF - Cell Transplantation

SN - 0963-6897

IS - 7

ER -