Pancreatic islets implanted in an irreversible electroporation generated extracellular matrix in the liver

Abstract

Background Pancreatic islet transplantation via infusion through the portal vein, has become an established clinical treatment for patients with type 1 diabetes. Because the engraftment efficiency is low, new approaches for pancreatic islets implantation are sought. The goal of this study is to explore the possibility that a non-thermal irreversible electroporation (NTIRE) decellularized matrix in the liver could be used as an engraftment site for pancreatic islets. Materials and methods Pancreatic islets or saline controls were injected at sites pre-treated with NTIRE in the livers of 7 rats, 16 hours after NTIRE treatment. Seven days after the NTIRE treatment, islet graft function was assessed by detecting insulin and glucagon in the liver with immunohistochemistry. Results Pancreatic islets implanted into a NTIRE-treated volume of liver became incorporated into the liver parenchyma and produced insulin and glucagon in 2 of the 7 rat livers. Potential reasons for the failure to observe pancreatic islets in the remaining 5/7 rats may include local inflammatory reaction, graft rejection, low numbers of starting islets, timing of implantation. Conclusions This study shows that pancreatic islets can become incorporated and function in an NTIRE-generated extracellular matrix niche, albeit the success rate is low. Advances in the field could be achieved by developing a better understanding of the mechanisms of failure and ways to combat these mechanisms.

Decellularization of Dense Regular Connective Tissue—Cellular and Molecular Modification with Applications in Regenerative Medicine

“…Some researchers apply it in various tissues because of its safety and simplicity, which make it possible to process in situ [ 93 ]. However, this technique is characterized as insufficient and causes increased inflammation in in vivo analysis [ 94 ]. The technique is used mainly to implement autologous grafts or in situ procedures, which are performed even on DRCT, while maintaining full strength efficiency of the structure [ 95 , 96 ].…”