Islet culture and counter-culture

Abstract

The publication of the Edmonton protocol caused a lot of excitement by reporting an almost overnight improvement in the rate of success of clinical islet of Langerhans transplantation [1]. Conventional wisdom holds that steroid-free immunosuppression and an increased transplanted islet mass, thanks to the use of multiple donors for each recipient, were the key determinants for the success of the Edmonton protocol. However, the protocol incorporated several additional strategies in the effort to improve the results of the method. One of these was the transplantation of freshly isolated islets within 2 h of the end of the isolation procedure [1,2]. This approach was novel, but based on intuition rather than on hard data. Indeed, in the previous years, islet preparations were commonly cultured prior to transplantation [3]. In the wake of the Edmonton report, many islet transplant centers attempted to reproduce its results by implementing the same protocol, including immediate transplantation of fresh islets, as was the case in the first ever multicenter trial of islet transplantation, funded by the Immune Tolerance Network [2]. There are, however, obvious logistical advantages in culturing islets prior to transplantation: it provides flexibility in the organization and planning of the procedure, which involves interventional radiology access and anesthesiology standby, and it allows the pooling of islet preparations sequentially isolated from different donor pancreata, to increase the islet graft functional mass. Indeed, it could be shown that transplantation of cultured islets could lead to seemingly similar success rates as those described by the Edmonton group [4,5]. The question thus arises whether culturing islets for a period of time could have a beneficial or detrimental impact on islet viability and function, and on what mechanistic basis. This question is addressed by Dr. Ihm et al. in a recent issue of Transplant International [6] [Correction added after publication 31 March 2009: in the preceding sentence, this issue was corrected to a recent issue]. This is an important question and it is noteworthy that this is one of very few publications that have addressed this topic studying human islets. Results obtained in animal models may not necessarily be extrapolated to the human, because of the species-specific impact of culture on islet function [7]. The authors show that short-term culture has a beneficial effect on islet vitality and viability. Two-day culture increased islet cell ATP contents and decreased the activity of protein kinases involved in pro-apoptotic signalling. These positive findings are balanced by the increased expression of certain pro-inflammatory genes induced by short-term culture. What matters to the islet transplant community, however, is the overall impact of short-term culture on in vivo islet function. It is well known and a matter of concern that culturing islets leads to a loss of function and mass Correspondence Thierry Berney MD, MSc, Division of Visceral/ Transplantation Surgery, Geneva University Hospitals, 24 rue MIcheli-du-Crest, CH-1211 Geneva 14. Tel.: +41 22 37 23 404; fax: +41 22 37 27 707; e-mail: thierry. berney@hcuge.ch