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THE HUMAN PANCREAS AS A SOURCE OF PRO-TOLEROGENIC EXTRACELLULAR MATRIX SCAFFOLD FOR A NEW GENERATION BIO-ARTIFICIAL ENDOCRINE PANCREAS #MMPMID26649588
Ann Surg 2016[Jul]; 264 (1): 169-79 PMID26649588show ga
OBJECTIVE: Our study aims at producing acellular extracellular matrix scaffolds from the human pancreas (hpaECMs), as a first critical step towards the production of a new generation, fully human-derived bio-artificial endocrine pancreas (BAEP). In this BAEP, the hardware will be represented by hpaECMs, while the software will consist in the cellular compartment generated from patient?s own cells. SUMMARY BACKGROUND DATA: 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 (GFs) 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 (hPPEC). RESULTS: Results show that hpaECMs can be successfully and consistently produced from human pancreata, maintain their innate molecular and spatial framework and stiffness, as well as vital GFs. 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 BAEP.