A Prevascularized Sinus Tract on the Liver Surface for Islet Transplantation

Abstract

Background. The lack of a suitable transplantation site has become a bottleneck restricting the development of islet transplantation. Methods. In this study, for the first time, a prevascularized sinus tract (PST) for islet transplantation was constructed in a mouse model by temporarily embedding a 4× silk thread between the liver surface and the attached decellularized human amniotic membrane. After which, the characteristics of the PST and the function of the islet graft within the PST were evaluated. Results. The results showed that PST was lined with granulation tissue, the blood vessel density of the local tissue increased, and proangiogenic proteins were upregulated, which mimics the microenvironment of the islets in the pancreas to a certain extent. Transplantation of ~200 syngeneic islets into the PST routinely reversed the hyperglycemia of the recipient mice and maintained euglycemia for >100 d until the islet grafts were retrieved. The islet grafts within the PST achieved better results to those in the nonprevascularized control groups and comparable results to those under the kidney capsule with respect to glycemic control and glucose tolerance. Conclusions. By attaching a decellularized human amniotic membrane to the surface of mouse liver and temporarily embedding a 4× silk thread, the PST formed on the liver surface has a favorable local microenvironment and is a potential clinical islet transplantation site.

Impact of Prevascularization on Immunological Environment and Early Engraftment in Subcutaneous Islet Transplantation

“…Adequate blood flow is essential for successful islet engraftment 9 ; however, blood supply in the subcutaneous space is limited. Various strategies to enhance blood flow have been explored, including the creation of a prevascularized site through the placement of a vascular access catheter, 10 use of scaffolds to promote angiogenesis, 11 , 12 development of transferrable microvascular meshes, 13 incorporation of a device-free islet viability matrix, 14 use of macroencapsulation devices, 8 formation of vascularized β-cell spheroid tissue through a 3-dimensional layer-by-layer cell-coating technique, 15 and delivery of exogenous growth factors via biomaterials.…”