Pancreatic acellular matrix supports islet survival and function in a synthetic tubular device: In vitro and in vivo studies

Abstract

Abstract. Increasing pancreatic islet survival and function is a starting point for obtaining a valuable bioartificial pancreas for the treatment of type 1 diabetes. In this context, decellularized matrices, obtained after the removal of tissue cellular part, are known to support in vitro adhesion, growth, and function of several cell types. We demonstrate that a homologous acellular pancreatic matrix is a suitable scaffold for rat islet cultures maintaining their long-term viability and function. Islets adhered to the pancreatic matrix showed a constant glucose-induced insulin release during long-term in vitro incubation, while islets cultured without a matrix or on the liver matrix showed a progressive reduction. In order to obtain implantable devices, acellular matrix/islet cultures were entrapped into poly(vinyl alcohol) (PVA)/ poly(ethylene glycol) (PEG) tubes obtained by the freezing/thawing procedure. Under this condition, an in vitro constant insulin release was detected. The devices were then implanted into diabetic rats where reduced insulin requirement was noted suggesting insulin secretory activity of islets contained in the device. Indeed, immunofluorescence confirmed the presence of insulin-and glucagon-producing cells into the explanted devices. These data show that PVA/PEG semi-permeable membrane can obtain devices that restore, at least in part, insulin secretion.

Decellularized Pancreas Matrix Scaffolds for Tissue Engineering Using Ductal or Arterial Catheterization

“…Successful decellularization involves removing all cells while preserving ECM components as well as a proper vasculature similar to the native tissue. Various perfusion decellularization protocols have been previously applied on the rodent, pig, and human pancreas [De Carlo et al, 2010;Goh et al, 2013].…”

Bioengineering the Pancreas: Cell-on-Scaffold Technology

“…Rats were then made diabetic and PVA/PEG devices (containing islets and matrix) were implanted. Results have demonstrated, in an in-vivo follow-up up to 6 weeks, how pancreatic devices reacted to glucose acute stimula with insulin delivery and a decreasing dose of daily insulin needed to maintain the euglycaemic condition [120]. To our knowledge, in the same year, Ott's lab proposed for the first time a rat pancreatic whole pancreas scaffold (obtained via detergent perfusion) afterwards seeded with human islets and supporting human MSCs.…”

Advances in Regenerative Medicine

“…Recent developments in encapsulation methodologies include the application of bioactive hydrogels with functionalized moieties designed to improve -cell survival and secretion of insulin (Lin and Anseth 2009) as well as to modulate inflammation . Implantation of PEG tubes containing rat islet cultures maintained on acellular pancreatic matrix was observed to lead to partial rescue of insulin secretory activity (De Carlo et al, 2010). Alternatively, pancreatic islet cells may be expanded through growth over polyglycolic acid (PGA) scaffolds.…”