Developing a pancreatic ECM-based 3D microencapsulation platform for diabetes therapy

Encapsulation of insulin–producing cells (IPCs) has been widely investigated to improve cell transplantation outcomes in diabetic patients.¹ However, major hurdles impede the technology from reaching the clinic, some of which being the limited survival of isolated beta cells and the inability of polymers used in the encapsulation process to mimic the natural pancreatic niche.² To surmount these obstacles, we present a unique microencapsulation platform incorporating a natural bioactive material: porcine pancreatic extracellular matrix (ECM). We hypothesize that the incorporation of this material will provide the encapsulated IPCs with the required natural support for their long-term biological activity.

ECM-based encapsulation platforms were designed for each of two cell types - pancreatic islets, the gold standard of diabetes-cell-based therapy, and induced pluripotent stem cells (iPSCs), a possible source for IPC derivation. Each of the cell types was seeded on ECM gels or encapsulated in the ECM-based systems. Encapsulated hiPSCs proliferated within the ECM microcapsules, forming spherical aggregates. Eight weeks following transplantation to healthy mice, encapsulated hiPSCs remained viable and no evidence of cell leakage from the capsules was observed. Electron microscopy revealed that gel-seeded islets adhere to the ECM. Furthermore, islet metabolic rate was significantly higher on the ECM gel compared to the control and increased proportionately to the ECM concentration. ECM-encapsulated islets remained viable in-vitro for more than two months post encapsulation. Moreover, two weeks following transplantation to healthy mice, retrieved encapsulated islets showed functional insulin expression.

Our findings demonstrate that the microenvironment within the ECM-microcapsules promotes cell proliferation and function and overcomes islets` naturally poor survival rates post isolation. Therefore, ECM-based microencapsulation has the potential to alter the landscape of beta-cell replacement therapy, paving the way for a more comprehensive future treatment for diabetes.

References:

1. Calafiore, R. & Basta, G. Clinical application of microencapsulated islets: Actual prospectives on progress and challenges. Advanced Drug Delivery Reviews (2013). doi:10.1016/j.addr.2013.09.020
2. Robles, L., Storrs, R., Lamb, M., Alexander, M. & Lakey, J. R. T. Current status of islet encapsulation. Cell Transplantation 23, 1321–1348 (2014).