Donor pancreas conditions that preserve therapeutic potential of human islet cell preparations

Donor islet cell transplantation can restore a functional beta cell mass (FBM) in diabetes but its metabolic effect remains variable and limited in time. This depends in part on the beta cell mass of the islet cell preparation and its ability to form and maintain a FBM. In this thesis, we use in vitro measures of the islet cell graft to identify conditions that preserve beta cell mass during pancreas procurement and preservation.
Quantification of beta cell mass by its number allowed us to demonstrate its independent correlation with warm ischemia time after circulatory death, while this was not the case when islet cell isolation yield was only quantified as islet equivalents. While donation after controlled circulatory death (DCD III) leads to a 30% reduction in beta cell yield, limiting warm ischemia time and using IGL-1 as cold preservation solution were identified as conditions that preserved beta cell yield. Under these conditions, donation after euthanasia (DCD V) was even associated with a higher beta cell yield than matched DCD III or donors after brain death (DBD).
We also used an hyperglycemic clamp test to determine functional beta cell mass after autologous islet cell transplantation and demonstrated its correlation with the beta cell mass of the autograft and FBM before pancreatectomy. As such it can be used as part of a multimodal risk assessment when considering and/or counselling patients for pancreatectomy and autologous islet cell transplantation.
In summary, using beta cell number as an intermediary endpoint for restoring a functional beta cell mass, we identified conditions that allow extending the available donor pool of donors after brain death with donors after controlled circulatory death and after euthanasia. It’s relationship with FBM is illustrated in allogenic (DCD V) and autologous islet cell transplantation but requires further research, which should also take into consideration its functional state.