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 native milieu 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. Encapsulated hiPSCs proliferated within the ECM microcapsules for at least 21 days in culture, forming spherical aggregates. Eight weeks following implantation within healthy C57BL/6 mice, encapsulated hiPSCs sustained their viability with no evidence of cell leakage from the capsules into the surrounding tissue. ECM-encapsulated murine islets remained viable and showed functional insulin expression in-vitro for more than five weeks post encapsulation. Moreover, when encapsulated with mesenchymal stem cells which were previously shown to promote islet functionality,³ islet insulin secretion was significantly increased.

Our findings demonstrate that the microenvironment within the ECM-microcapsules supports cell viability and function and overcomes the natural poor survival rates of islets post isolation. It also enables the in-vivo isolation and safe retrieval of implanted iPSC-derived cells. Therefore, pancreatic 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).
3. de Souza, B. M. et al. Effect of co-culture of mesenchymal stem/stromal cells with pancreatic islets on viability and function outcomes: a systematic review and meta-analysis. Islets 9, 30–42 (2017).