Clinical islet transplantation has undergone profound changes since the turn of the millenium. Application of the approaches proposed by the seminal publication of the University of Alberta have been able to achieve consistent insulin-independence in a vast majority of islet transplant recipients. Islet graft function, even in the absence of insulin independence, procures glycemic stability and is able to control progression of diabetes complications. The field has seen the following progress and is facing the following issues and challenges (non-exhaustive list) :
In contrast to vascularized pancreas, islet transplantation is mostly performed as islet transplantation alone (ITA), and activity and results of islet transplantation in uremic patients with T1DM do not match those of ITA.
The application of appropriate immunosuppressive strategies, targeting both adaptive (T-cell depletion, co-stimulatory blockade) and innate immunity (TNF-a blockade,…) currently yields rates of insulin independence of 50% at 5 years.
These results are obtained as a rule at a cost of multiple-donor transplantation, highlighting the progress that must still be made in improving islet engraftment, primarily by targeting all compartments of innate immunity (coagulation factors, inflammatory cells, cyto/chemokines,…) and exploring novel sites for islet graft implantation.
The islet isolation procedure still remains technically challenging and is characterized by suboptimal rates of success. This has been partly addressed by the creation of islet transplantation network around centralized islet producing expert facilities (GRAGIL, Nordic network, UK consortium,…). Refining the islet isolation procedure and developing new pancreas preservation strategies remain a work in progress.
Allocation of donor pancreases for islet versus vascularized transplantation must be redefined in order to direct high-quality organs toward patients with T1DM in need of a transplant regardless of type of beta-cell replacement.
While clinical islet transplantation has demonstrated its value, it is covered by the health care system only in a small number of countries (Canada, Switzerland, UK,..). Because of absence of reimbursement, islet transplant activity has dramatically diminished in the USA. Unveiling of the long-awaited resuts of the CIT trials will hopefully unlock this situation in the USA, and hence in other countries.
While it is obvious that allogeneic islet transplantation will not bring the solution to type 1 diabetes, it is equally clear that all efforts made in the field will contribute to the goal of finding a cure to the disease through cell therapy strategies, whatever the sources of regulated insulin-producing tissues or the delivering tools utilized.
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