Decellularized human pancreatic extracellular matrix-based physiomimetic microenvironment for human islet culture.

A strategy that seeks to combine the biophysical properties of inert encapsulation materials like alginate with the biochemical niche provided by pancreatic extracellular matrix (ECM)-derived biomaterials, could provide a physiomimetic pancreatic microenvironment for maintaining long-term islet viability and function in culture. Herein, we have demonstrated that incorporating human pancreatic decellularized ECM within alginate microcapsules results in a significant increase in Glucose Stimulation Index (GSI) and total insulin secreted by encapsulated human islets, compared to free islets and islets encapsulated in only alginate. ECM supplementation also resulted in long-term (58 days) maintenance of GSI levels, similar to that observed in free islets at the first time point (day 5). At early time points in culture, ECM promoted gene expression changes through ECM- and cell adhesion-mediated pathways, while it demonstrated a mitochondria-protective effect in the long-term. STATEMENT OF SIGNIFICANCE: The islet isolation process can damage the islet extracellular matrix, resulting in loss of viability and function. We have recently developed a detergent-free, DI-water based method for decellularization of human pancreas to produce a potent solubilized ECM. This ECM was added to alginate for microencapsulation of human islets, which resulted in significantly higher stimulation index and total insulin production, compared to only alginate capsules and free islets, over long-term culture. Using ECM to preserve islet health and function can improve transplantation outcomes, as well as provide novel materials and platforms for studying islet biology in microfluidic, organ-on-a-chip, bioreactor and 3D bioprinted systems.

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Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Giuseppe Orlando reports a relationship with Seraxis Inc. that includes: board membership. Giuseppe Orlando is also a co-inventor on “Minimal Processing Method for Decellularization of Tissues” filed on May 8, 2020 as US 17/607,995 (patent pending); “Capsule Comprising Insulin-Secreting Cells for Treating Diabetes” filed on September 29, 2021 as USSN: 17/599,895 (patent pending); and “Organ/Tissue Decellularization, Framework Maintenance and Recellularization” issued on May 16, 2023 as US 11,648,335.