The human pancreas as a source of protolerogenic extracellular matrix scaffold for a new-generation bioartificial endocrine pancreas

Andrea Peloso, Luca Urbani, Paolo Cravedi, Ravi Katari, Panagiotis Maghsoudlou, Mario Enrique Alvarez Fallas, Valeria Sordi, Antonio Citro, Carolina Purroy, Guoguang Niu, John P. Mcquilling, Sivanandane Sittadjody, Alan C. Farney, Samy S. Iskandar, Joao P. Zambon, Jeffrey Rogers, Robert J. Stratta, Emmanuel C. Opara, Lorenzo Piemonti, Cristina M. FurduiShay Soker, Paolo De Coppi, Giuseppe Orlando

Research output: Contribution to journalArticle

Abstract

Objectives: Our study aims at producing acellular extracellular matrix scaffolds from the human pancreas (hpaECMs) as a first critical step toward the production of a new-generation, fully human-derived bioartificial endocrine pancreas. In this bioartificial endocrine pancreas, the hardware will be represented by hpaECMs, whereas the software will consist in the cellular compartment generated from patient's own cells. Background: Extracellular matrix (ECM)-based scaffolds obtained through the decellularization of native organs have become the favored platform in the field of complex organ bioengineering. However, the paradigm is now switching from the porcine to the human model. Methods: To achieve our goal, human pancreata were decellularized with Triton-based solution and thoroughly characterized. Primary endpoints were complete cell and DNA clearance, preservation of ECM components, growth factors and stiffness, ability to induce angiogenesis, conservation of the framework of the innate vasculature, and immunogenicity. Secondary endpoint was hpaECMs' ability to sustain growth and function of human islet and human primary pancreatic endothelial cells. Results: Results show that hpaECMs can be successfully and consistently produced from human pancreata and maintain their innate molecular and spatial framework and stiffness, and vital growth factors. Importantly, hpaECMs inhibit human naïve CD4 + T-cell expansion in response to polyclonal stimuli by inducing their apoptosis and promoting their conversion into regulatory T cells. hpaECMs are cytocompatible and supportive of representative pancreatic cell types. Discussion: We, therefore, conclude that hpaECMs has the potential to become an ideal platform for investigations aiming at the manufacturing of a regenerative medicine-inspired bioartificial endocrine pancreas.
Original languageEnglish
Pages (from-to)169 - 179
Number of pages11
JournalAnnals of Surgery
Volume264
Issue number1
DOIs
Publication statusPublished - Jul 1 2016

Fingerprint

Islets of Langerhans
Extracellular Matrix
Pancreas
Intercellular Signaling Peptides and Proteins
Bioengineering
Regenerative Medicine
Regulatory T-Lymphocytes
Swine
Software
Endothelial Cells
Apoptosis
T-Lymphocytes
DNA
Growth

Keywords

  • angiogenesis
  • bioartificial pancreas
  • decellularization
  • diabetes
  • discarded pancreas
  • ECM
  • growth factors
  • organ bioengineering and regeneration
  • scaffold
  • β-cell replacement

ASJC Scopus subject areas

  • Surgery

Cite this

The human pancreas as a source of protolerogenic extracellular matrix scaffold for a new-generation bioartificial endocrine pancreas. / Peloso, Andrea; Urbani, Luca; Cravedi, Paolo; Katari, Ravi; Maghsoudlou, Panagiotis; Fallas, Mario Enrique Alvarez; Sordi, Valeria; Citro, Antonio; Purroy, Carolina; Niu, Guoguang; Mcquilling, John P.; Sittadjody, Sivanandane; Farney, Alan C.; Iskandar, Samy S.; Zambon, Joao P.; Rogers, Jeffrey; Stratta, Robert J.; Opara, Emmanuel C.; Piemonti, Lorenzo; Furdui, Cristina M.; Soker, Shay; De Coppi, Paolo; Orlando, Giuseppe.

In: Annals of Surgery, Vol. 264, No. 1, 01.07.2016, p. 169 - 179.

Research output: Contribution to journalArticle

Peloso, A, Urbani, L, Cravedi, P, Katari, R, Maghsoudlou, P, Fallas, MEA, Sordi, V, Citro, A, Purroy, C, Niu, G, Mcquilling, JP, Sittadjody, S, Farney, AC, Iskandar, SS, Zambon, JP, Rogers, J, Stratta, RJ, Opara, EC, Piemonti, L, Furdui, CM, Soker, S, De Coppi, P & Orlando, G 2016, 'The human pancreas as a source of protolerogenic extracellular matrix scaffold for a new-generation bioartificial endocrine pancreas', Annals of Surgery, vol. 264, no. 1, pp. 169 - 179. https://doi.org/10.1097/SLA.0000000000001364
Peloso, Andrea ; Urbani, Luca ; Cravedi, Paolo ; Katari, Ravi ; Maghsoudlou, Panagiotis ; Fallas, Mario Enrique Alvarez ; Sordi, Valeria ; Citro, Antonio ; Purroy, Carolina ; Niu, Guoguang ; Mcquilling, John P. ; Sittadjody, Sivanandane ; Farney, Alan C. ; Iskandar, Samy S. ; Zambon, Joao P. ; Rogers, Jeffrey ; Stratta, Robert J. ; Opara, Emmanuel C. ; Piemonti, Lorenzo ; Furdui, Cristina M. ; Soker, Shay ; De Coppi, Paolo ; Orlando, Giuseppe. / The human pancreas as a source of protolerogenic extracellular matrix scaffold for a new-generation bioartificial endocrine pancreas. In: Annals of Surgery. 2016 ; Vol. 264, No. 1. pp. 169 - 179.
@article{e9917ca952de45dc973904d737749924,
title = "The human pancreas as a source of protolerogenic extracellular matrix scaffold for a new-generation bioartificial endocrine pancreas",
abstract = "Objectives: Our study aims at producing acellular extracellular matrix scaffolds from the human pancreas (hpaECMs) as a first critical step toward the production of a new-generation, fully human-derived bioartificial endocrine pancreas. In this bioartificial endocrine pancreas, the hardware will be represented by hpaECMs, whereas the software will consist in the cellular compartment generated from patient's own cells. Background: Extracellular matrix (ECM)-based scaffolds obtained through the decellularization of native organs have become the favored platform in the field of complex organ bioengineering. However, the paradigm is now switching from the porcine to the human model. Methods: To achieve our goal, human pancreata were decellularized with Triton-based solution and thoroughly characterized. Primary endpoints were complete cell and DNA clearance, preservation of ECM components, growth factors and stiffness, ability to induce angiogenesis, conservation of the framework of the innate vasculature, and immunogenicity. Secondary endpoint was hpaECMs' ability to sustain growth and function of human islet and human primary pancreatic endothelial cells. Results: Results show that hpaECMs can be successfully and consistently produced from human pancreata and maintain their innate molecular and spatial framework and stiffness, and vital growth factors. Importantly, hpaECMs inhibit human na{\"i}ve CD4 + T-cell expansion in response to polyclonal stimuli by inducing their apoptosis and promoting their conversion into regulatory T cells. hpaECMs are cytocompatible and supportive of representative pancreatic cell types. Discussion: We, therefore, conclude that hpaECMs has the potential to become an ideal platform for investigations aiming at the manufacturing of a regenerative medicine-inspired bioartificial endocrine pancreas.",
keywords = "angiogenesis, bioartificial pancreas, decellularization, diabetes, discarded pancreas, ECM, growth factors, organ bioengineering and regeneration, scaffold, β-cell replacement",
author = "Andrea Peloso and Luca Urbani and Paolo Cravedi and Ravi Katari and Panagiotis Maghsoudlou and Fallas, {Mario Enrique Alvarez} and Valeria Sordi and Antonio Citro and Carolina Purroy and Guoguang Niu and Mcquilling, {John P.} and Sivanandane Sittadjody and Farney, {Alan C.} and Iskandar, {Samy S.} and Zambon, {Joao P.} and Jeffrey Rogers and Stratta, {Robert J.} and Opara, {Emmanuel C.} and Lorenzo Piemonti and Furdui, {Cristina M.} and Shay Soker and {De Coppi}, Paolo and Giuseppe Orlando",
year = "2016",
month = "7",
day = "1",
doi = "10.1097/SLA.0000000000001364",
language = "English",
volume = "264",
pages = "169 -- 179",
journal = "Annals of Surgery",
issn = "0003-4932",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - The human pancreas as a source of protolerogenic extracellular matrix scaffold for a new-generation bioartificial endocrine pancreas

AU - Peloso, Andrea

AU - Urbani, Luca

AU - Cravedi, Paolo

AU - Katari, Ravi

AU - Maghsoudlou, Panagiotis

AU - Fallas, Mario Enrique Alvarez

AU - Sordi, Valeria

AU - Citro, Antonio

AU - Purroy, Carolina

AU - Niu, Guoguang

AU - Mcquilling, John P.

AU - Sittadjody, Sivanandane

AU - Farney, Alan C.

AU - Iskandar, Samy S.

AU - Zambon, Joao P.

AU - Rogers, Jeffrey

AU - Stratta, Robert J.

AU - Opara, Emmanuel C.

AU - Piemonti, Lorenzo

AU - Furdui, Cristina M.

AU - Soker, Shay

AU - De Coppi, Paolo

AU - Orlando, Giuseppe

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Objectives: Our study aims at producing acellular extracellular matrix scaffolds from the human pancreas (hpaECMs) as a first critical step toward the production of a new-generation, fully human-derived bioartificial endocrine pancreas. In this bioartificial endocrine pancreas, the hardware will be represented by hpaECMs, whereas the software will consist in the cellular compartment generated from patient's own cells. Background: Extracellular matrix (ECM)-based scaffolds obtained through the decellularization of native organs have become the favored platform in the field of complex organ bioengineering. However, the paradigm is now switching from the porcine to the human model. Methods: To achieve our goal, human pancreata were decellularized with Triton-based solution and thoroughly characterized. Primary endpoints were complete cell and DNA clearance, preservation of ECM components, growth factors and stiffness, ability to induce angiogenesis, conservation of the framework of the innate vasculature, and immunogenicity. Secondary endpoint was hpaECMs' ability to sustain growth and function of human islet and human primary pancreatic endothelial cells. Results: Results show that hpaECMs can be successfully and consistently produced from human pancreata and maintain their innate molecular and spatial framework and stiffness, and vital growth factors. Importantly, hpaECMs inhibit human naïve CD4 + T-cell expansion in response to polyclonal stimuli by inducing their apoptosis and promoting their conversion into regulatory T cells. hpaECMs are cytocompatible and supportive of representative pancreatic cell types. Discussion: We, therefore, conclude that hpaECMs has the potential to become an ideal platform for investigations aiming at the manufacturing of a regenerative medicine-inspired bioartificial endocrine pancreas.

AB - Objectives: Our study aims at producing acellular extracellular matrix scaffolds from the human pancreas (hpaECMs) as a first critical step toward the production of a new-generation, fully human-derived bioartificial endocrine pancreas. In this bioartificial endocrine pancreas, the hardware will be represented by hpaECMs, whereas the software will consist in the cellular compartment generated from patient's own cells. Background: Extracellular matrix (ECM)-based scaffolds obtained through the decellularization of native organs have become the favored platform in the field of complex organ bioengineering. However, the paradigm is now switching from the porcine to the human model. Methods: To achieve our goal, human pancreata were decellularized with Triton-based solution and thoroughly characterized. Primary endpoints were complete cell and DNA clearance, preservation of ECM components, growth factors and stiffness, ability to induce angiogenesis, conservation of the framework of the innate vasculature, and immunogenicity. Secondary endpoint was hpaECMs' ability to sustain growth and function of human islet and human primary pancreatic endothelial cells. Results: Results show that hpaECMs can be successfully and consistently produced from human pancreata and maintain their innate molecular and spatial framework and stiffness, and vital growth factors. Importantly, hpaECMs inhibit human naïve CD4 + T-cell expansion in response to polyclonal stimuli by inducing their apoptosis and promoting their conversion into regulatory T cells. hpaECMs are cytocompatible and supportive of representative pancreatic cell types. Discussion: We, therefore, conclude that hpaECMs has the potential to become an ideal platform for investigations aiming at the manufacturing of a regenerative medicine-inspired bioartificial endocrine pancreas.

KW - angiogenesis

KW - bioartificial pancreas

KW - decellularization

KW - diabetes

KW - discarded pancreas

KW - ECM

KW - growth factors

KW - organ bioengineering and regeneration

KW - scaffold

KW - β-cell replacement

UR - http://www.scopus.com/inward/record.url?scp=84949464758&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84949464758&partnerID=8YFLogxK

U2 - 10.1097/SLA.0000000000001364

DO - 10.1097/SLA.0000000000001364

M3 - Article

VL - 264

SP - 169

EP - 179

JO - Annals of Surgery

JF - Annals of Surgery

SN - 0003-4932

IS - 1

ER -