Effect of the Embolization of Completely Unpurified Islets on Portal Vein Pressure and Hepatic Biochemistry in Clinical Practice

Abstract

Here we report on the impact of completely unpurified islet transplantation on the portal vein pressure (PVP) and the hepatic biochemistry in the peritransplant period and on follow-up. Type I diabetic patients underwent simultaneous kidney and islet transplantation. Islets were not purified from the acinar tissue to prevent loss of endocrine mass. Each patient received a mean 521,846 +/- 201,539.4 islet equivalents (7812.1 islet equivalents/kg/recipient). Immunosuppression and peritransplant medication were given according to the Giessen protocol. The islets were injected into the left hepatic lobe through the umbilical vein. PVP was recorded at time 0 and every 5 min throughout cell infusion. Liver function was assessed daily for the first 10 days, and on follow-up. Basal, peak, and final PVP were 12 +/- 3.8, 25.1 +/- 7.9, and 19.5 +/- 6.2 mmHg, respectively (basal vs. final, p < 0.05). Bilirubin, alkaline phosphatase, prothrombin time, and APTT stayed within normal range. Peak aspartate aminotransferase (AST), alanine aminotransferase (ALT), and serum amylase were 109.4 +/- 61.2 IU/L (basal vs. peak, not significant), 79.5 +/- 56.9 IU/L (basal vs. peak, not significant), and 887.5 +/- 153.6 IU/L (basal vs. peak, p = 0.02), respectively. In all cases AST, ALT, and amylase normalized within 6 days posttransplant and remained so on follow-up (longest control, 33 months posttransplant). Although the intrahepatic infusion of unpurified pancreatic islets affects both the portal vein pressure and the hepatic biochemical profile, this effect is transient and does not compromise the safety of the procedure.

Rapamycin does not adversely affect intrahepatic islet engraftment in mice and improves early islet engraftment in humans

“…29 Intrahepatic islet infusion is associated with an immediate blood-mediated inflammatory reaction, thrombosis and hepatic tissue ischemia. 20,[30][31][32][33][34][35][36][37][38][39][40][41] Kidney subcapsular transplantation or subcutaneous implantation are not intravascular and are, therefore, devoided of these complications. Thus, the mechanism of engraftment and islet survival are different and, although transplantation under the kidney capsule may be a useful model to study mechanisms of immune tolerance or neovasculogenesis, unlikely provides information relevant to islet engraftment in man.…”

Liver Natural Killer Cells Play a Role in the Destruction of Islets After Intraportal Transplantation

“…Although intraportal islet transplantation has its advantages, poor long-term clinical outcomes have raised the question whether the liver is the optimal site for islet survival (2)(3)(4). After intraportal islet transplantation, there is a rapid reduction in transplanted islet mass, presumably due to various factors such as the hypoxic condition of transplanted islets (5), mechanical damage by embolization of the portal vein (6), and antigen-nonspecific inflammatory events occurring at the transplant site shortly after transplantation (7)(8)(9)(10). Innate immune responses can also cause a loss of a large percentage of transplanted islets and is considered a major obstacle in islet transplantation (9 -11).…”

Skin Fibroblasts from Patients with Type 1 Diabetes (T1D) Can Be Chemically Transdifferentiated into Insulin-Expressing Clusters: A Transgene-Free Approach

“…Type 1 diabetes (T1D), which is a multifactorial autoimmune disease that is caused by β-cell destruction that leads to the deregulation of glucose homeostasis, has initially been treated by exogenous insulin therapy or through cellular replacement by a whole-pancreas transplant or by islet transplantation into the portal vein [1]. However, the low ratio of donors to recipients for cellular replacement requires more viable alternative treatments.…”