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The Human Pancreas as a Source of Protolerogenic Extracellular Matrix Scaffold for a New-generation Bioartificial Endocrine Pancreas
Open accessAbstract
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.
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“Thereby, dECM-based scaffolds are more biocompatible and confront less rejection rate compared to other implants [30–32].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [31]
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“dECM scaffolds affect CD4+ T cell maturation and differentiation to shift T cell polarization toward regulatory phenotype (T reg), an immunomodulatory subtype that downregulates T cell activity.”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [31]
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Metadata
- Authors
- Peloso, A., Urbani, L., Cravedi, P., Katari, R., Maghsoudlou, P., Fallas, M. E. A., Sordi, V., Citro, A., Purroy, C., Niu, G., McQuilling, J. P., Sittadjody, S., Farney, A. C., Iskandar, S. S., Zambon, J. P., Rogers, J., Stratta, R. J., Opara, E. C., Piemonti, L., Furdui, C. M., Soker, S., De Coppi, P., & Orlando, G.
- Affiliations
- Great Ormond Street Hospital (GB)
- ORCID
- Venue
- Annals of Surgery
- Published
- 2016-07
- Volume
- 264
- Issue
- 1
- Pages
- 169-179
- ISSN
- 0003-4932 (ISSN-L)
- PMC
- PMC4882269
- OpenAlex
- W2325796265
- Cited by
- 133
- References
- 30
- Citations by year
- 2025: 7 · 2024: 7 · 2023: 13 · 2022: 10 · 2021: 14 · 2020: 21 · 2019: 18 · 2018: 19 · 2017: 14 · 2016: 8
- FWCI
- 14.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Surgery (publishedVersion)
- PubMed (publishedVersion)
- Explore Bristol Research (publishedVersion)
- PubMed Central (acceptedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion, cc-by-nc-sa)
- UCL Discovery (University College London) (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- National Institute for Health and Care Research (RP_2014-04-046)
- National Institute of Allergy and Infectious Diseases (T32AI078892)
- National Institute of Biomedical Imaging and Bioengineering (T32EB014836)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- human pancreas, extracellular matrix scaffolds, decellularization, islet transplantation, regulatory T cells, CD4+ T cell apoptosis, immunogenicity, angiogenesis, tissue stiffness, growth factors, regenerative medicine
- MeSH terms
- Extracellular Matrix, Humans, Islets of Langerhans, Pancreas, Regeneration, Tissue Engineering, Organogenesis, Tissue Scaffolds
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