Studying ECM-microcapsules as a niche for the entrapment of pancreatic islets

Pancreatic islets microencapsulation has been studied for treating type 1 diabetes, thus aiming to help the islets cope with post-isolation and post-transplantation stress, and to provide them with a protective niche.1 The material used for the fabrication of the microcapsules, however, has a crucial role in mimicking the natural tissue and supporting the structural, biological, and mechanical properties of the islets. Therefore, we developed a microencapsulation platform based on a biocompatible bioactive material - porcine pancreatic extracellular matrix (ppECM).2 We hypothesize that microcapsules composed of ppECM can provide the encapsulated islets with a pancreatic microenvironment, thus granting them both structural and biological support, and contributing to their long-term viability and function in-vitro and in-vivo.

Islets were isolated from rats and encapsulated within ppECM microcapsules. The viability of the islets, their function, and the protective effect of the ppECM in hypoxic conditions were evaluated. Following encapsulation, the islets remained viable for at least 14 days, thus expressing insulin and glucagon. Furthermore, insulin secretion was shown to be glucose-responsive, indicating their proper function. On day 14 post-encapsulation, a significantly lower insulin level was secreted by alginate-encapsulated islets compared to ppECM-encapsulated or non-encapsulated islets. In addition, collagen I and collagen IV, which are known to be present in the pancreas, were expressed by ppECM-encapsulated islets. Furthermore, β-cells in the islets expressed Pdx1, which is required for their maintenance and survival in the mature pancreas. These findings demonstrate the beneficial effect of the ppECM-based microencapsulation which supports pancreatic rat islets and increases their viability and function.

1. Silva, A. I., Norton De Matos, A., Brons, I. G. & Mateus, M. An overview on the development of a bio-artificial pancreas as a treatment of insulin-dependent diabetes mellitus. Med. Res. Rev. 26, 181–222 (2006).

2. Chaimov, D. et al. Innovative encapsulation platform based on pancreatic extracellular matrix achieve substantial insulin delivery. J. Control. Release 257, 91–101 (2017).