The Human Pancreas as a Source of Protolerogenic Extracellular Matrix Scaffold for a New-generation Bioartificial Endocrine Pancreas
| Autor: | Samy S. Iskandar, Luca Urbani, Mario Enrique Alvarez Fallas, Panagiotis Maghsoudlou, Emmanuel C. Opara, Cristina M. Furdui, Andrea Peloso, Lorenzo Piemonti, Shay Soker, Giuseppe Orlando, Valeria Sordi, Jeffrey Rogers, Robert J. Stratta, Paolo Cravedi, Carolina Purroy, Antonio Citro, Sivanandane Sittadjody, Paolo De Coppi, Guoguang Niu, Ravi Katari, Joao Paulo Zambon, Alan C. Farney, John P. McQuilling |
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| Přispěvatelé: | Peloso, Andrea, Urbani, Luca, Cravedi, Paolo, Katari, Ravi, Maghsoudlou, Panagioti, 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, Pathology/molecular and cellular medicine |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Organogenesi Angiogenesis Xenotransplantation medicine.medical_treatment Organogenesis bioartificial pancrea 02 engineering and technology scaffold Regenerative medicine organ bioengineering and regeneration Article β-cell replacement Extracellular matrix 03 medical and health sciences Islets of Langerhans Tissue engineering Tissue Scaffold Journal Article medicine Pancrea Humans Regeneration Pancreas Decellularization ECM Tissue Engineering Tissue Scaffolds business.industry Research Support Non-U.S. Gov't Regeneration (biology) angiogenesi growth factor Islets of Langerhan 021001 nanoscience & nanotechnology Cell biology Extracellular Matrix 030104 developmental biology medicine.anatomical_structure diabete Immunology decellularization Surgery 0210 nano-technology business discarded pancrea Human |
| Zdroj: | Annals of surgery. 264(1) |
| ISSN: | 1528-1140 |
| Popis: | 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 naive 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. |
| Databáze: | OpenAIRE |
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