Rapport final
Definition of reference markers for therapeutic potential of human beta cells in preclinical transplantation - Jacobs-Tulleneers-Thevissen Daniel
Beta cell replacement using isolates prepared from deceased donor pancreases can improve metabolic control in type 1 diabetic patients after their implantation in the liver. Therapeutic potential of these beta cell implants depend on their number and functional statement at the moment of engraftment; these characteristics differ between isolates prepared from different donors and processed in different conditions.
We first used the number of living beta cells as outcome measure of pancreatic islet isolations from controlled donors after circulatory death (DCD III) and compared it to standard donors after brain death (DBD). While on average these organs yield a lower number of living beta cells than is the case for DBD, limiting the initial warm ischemia time typical for DCD III positively correlates to beta cell yield. We also observed that when preserving these organs using Institut Georges Lopez-1 preservation solution the numbers of beta cells that can be obtained are similar as for DBD.
We then used beta cell number, insulin purity and content and glucose stimulated insulin release and biosynthesis capacity as outcome markers for beta cell isolation from donors after euthanasia (DCD V), a subgroup of donors after circulatory arrest and compared it to those of DBD. For all outcome parameters, DCD V isolates are on average superior to those obtained from DBD.
This study allowed us to identify a number of donor and preservation characteristics that can lead to beta cell implants that exhibit markers for therapeutic capacity.