Time Course of Islet Loss after Intraportal Transplantation

Abstract

A high percentage of islets fail to survive intraportal transplantation, but the absolute amount and time course of this loss are uncertain. We have devised a technique to directly quantitate the number of surviving islets using simultaneous selective transplantation of islets and inert beads into the posterior lobes of the liver. Islet:bead ratio did not change significantly within the first 2 hours, but fell progressively thereafter, giving calculated islet survival rates of 89, 43, and 66% at days 1, 7 and 28, respectively. This technique provides a baseline from which to develop strategies to improve the survival of intraportally transplanted islets.

Highly Selective Intraportal Transplantation of Pancreatic Islets

“…Following the transplantation of 500 islets the average size of the engrafted islets is comparable to what we have previously reported [27,28]. However, in the 1000 islet transplant groups, the fact that the islets are twice as large is intriguing.…”

“…One might speculate therefore that the greater hypoxic injury to the liver in response to a greater mass of tissue embolized into the liver might induce a greater growth factor response and hence induce b-cell proliferation to a greater extent. However, we did not see this when we transplanted 500 islets with 500 beads simultaneously [28]. Assuming that islet neogenesis plays no significant part in islet remodeling following transplantation, successful engraftment would depend largely on the transplanted b-cell mass, which is consistent with what has been described clinically [30,31].…”

A Calpain Inhibitor Enhances the Survival of Schwann CellsIn Vitroand after Transplantation into the Injured Spinal Cord

“…In the CNS, transplant survival has been quantified following implantation of neural progenitor cells into the injured spinal cord (Marsala et al, 2004), and brain (Bakshi et al, 2005), and implantation of dopaminergic neurons into models of Parkinson's disease (Barker et al, 1996;Emgard et al, 1999;Marsala et al, 2004). Outside of the CNS, transplant survival has been quantified following implantation of cardiomyocytes into the heart (Reinecke and Murry, 2002), and pancreatic islet cells into the liver (Pawelec et al, 2008).…”

Amyloid Formation in Human Islets Is Enhanced by Heparin and Inhibited by Heparinase

“…Heparin is used in clinical islet transplantation to prevent loss of islets by thrombosis and the instant bloodmediated inflammatory reaction (IBMIR) (22). Heparin (23) or its low molecular weight form, enoxaparin (24), has been administered to patients up to 7 days following islet transplantation.…”