No abstract

Emergent technologies of regenerative medicine have the potential to overcome the limitations of organ transplantation by supplying tissues and organs bioengineered in the laboratory. Pancreas bioengineering requires a scaffold that approximates the biochemical, spatial and vascular relationships of the native extracellular matrix (ECM). We describe the generation of a whole organ, three-dimensional pancreas scaffold using acellular porcine pancreas. Imaging studies confirm that our protocol effectively removes cellular material while preserving ECM proteins and the native vascular tree. The scaffold was seeded with human stem cells and porcine pancreatic islets, demonstrating that the decellularized pancreas can support cellular adhesion and maintenance of cell functions. These findings advance the field of regenerative medicine towards the development of a fully functional, bioengineered pancreas capable of establishing and sustaining euglycemia and may be used for transplantation to cure diabetes mellitus.

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.

No abstract