LIQUEFIED PANCREATIC ECM : A NOVEL ENCAPSULATION PLATFORM FOR DIABETES THERAPY

Despite the large potential of beta cells encapsulation for diabetes therapy, and the extensive knowledge gained in the field, severe hurdles impede their clinical application. Those include the limited longevity of beta cells, and the polymers used, which provide immunological and mechanical protection, but do not mimic the cell biological niche.

Extracellular matrix (ECM) plays a vital role in intracellular signalling pathways. Moreover, ECM-based materials were shown to improve islet culture and insulin secretion.

Therefore, the aim of this study was to develop a unique cell microencapsulation platform, which is based on isolated porcine pancreatic ECM.

Human mesenchymal stem cells and liver cells, which were induced to transdifferentiate into insulin producing cells, were encapsulated in gelled ECM, produced by enzymatic decellularization and liquefaction of porcine pancreatic tissue.

The newly-developed ECM-microencapsulation system significantly improved cells differentiation and insulin secretion (up to 5-fold increase comparing to transduced non-encapsulated cells, p˂0.001). Moreover, the ECM-encapsulated cells were immunologically silent, as concluded from the negligible levels of pro-inflammatory cytokines in the peripheral blood and the normal values of complete blood count.

Most importantly, transplantation of approximately 5.5x10⁵ ECM-encapsulated transduced cells to diabetic mice significantly ameliorated hyperglycemia for up to four weeks. This was demonstrated in reduced blood glucose levels which were maintained less than 300 mg/dl through all the experiment, as well as the fructosamine levels, which were reduced to levels of healthy, non-diabetic mice (p˂0.005). Similarly, treated mice responded to glucose tolerance test with a clearance rate that paralleled that of healthy mice.

Altogether, the advantages of this ECM-encapsulation system, clearly point at our ECM-based microencapsulation platform as a promising prospective cell-based therapy for the treatment of diabetes.