Rat Islet pECM Hydrogel-Based Microencapsulation: A Protective Niche for Xenotransplantation

TL;DR

This study introduces a new method using decellularized pig pancreatic tissue to create protective microcapsules for rat islets, which could improve islet transplantation for diabetes treatment.

Contribution

The use of decellularized porcine pancreatic extracellular matrix (pECM) as a standalone material for islet microencapsulation is novel.

Findings

pECM microcapsules preserved islet viability and function better than alginate controls over two weeks.

pECM microcapsules reduced islet apoptosis and improved recovery under hypoxic conditions.

In vivo tests showed pECM microcapsules were biocompatible with minimal immune response.

Abstract

Type 1 diabetes (T1D) is caused by autoimmune-mediated destruction of pancreatic β-cells, resulting in insulin deficiency. While islet transplantation presents a potential therapeutic approach, its clinical application is impeded by limited donor availability and the risk of immune rejection. This study proposes an innovative islet encapsulation strategy that utilizes decellularized porcine pancreatic extracellular matrix (pECM) as the sole biomaterial to engineer bioactive, immunoprotective microcapsules. Rat islets were encapsulated within pECM-based microcapsules using the electrospray technology and were compared to conventional alginate-based microcapsules in terms of viability, function, and response to hypoxic stress. The pECM microcapsules maintained a spherical morphology, demonstrating mechanical robustness, and preserving essential ECM components (collagen I/IV, laminin, fibronectin). Encapsulated islets exhibited sustained viability and superior insulin secretion over a two-week period compared to alginate controls. The expression of key β-cell transcription factors (PDX1, MAFA) and structural integrity were preserved. Under hypoxic conditions, pECM microcapsules significantly reduced islet apoptosis, improved structural retention, and promoted functional recovery, likely due to antioxidant and ECM-derived cues inherent to the pECM. In vivo transplantation in immunocompetent mice confirmed the biocompatibility of pECM microcapsules, with minimal immune responses, stable insulin/glucagon expression, and no adverse systemic effects. These findings position pECM-based microencapsulation as a promising strategy for creating immunoprotective, bioactive niches for xenogeneic islet transplantation, with the potential to overcome current limitations in cell-based diabetes therapy.

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