Transplantation of the islets of Langerhans
The islets of Langerhans are microorganisms that populate the human pancreas and that produce different types of hormones that control blood sugar levels, including insulin. Cell therapy approaches for the treatment of type 1 diabetes are based on the evidence that these micro-organs must be destroyed or are malfunctioning and therefore their regeneration or replacement can cure the disease.
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Islet transplantation of Langerhans is a therapy based on the extraction of these microorganisms from the pancreas of organ donors and their infusion into the liver of subjects with diabetes in order to build a puzzle organ, i.e. a liver capable of acquiring some functions of the pancreas.
Langerhans islet transplantation was recognized in 2022 within the ISS National Guidelines System as a treatment to be evaluated in individuals with unstable diabetes despite the use of the best insulin therapy possible. This recognition comes about 32 years after the first experimental approaches in humans and constitutes an example of regenerative medicine that has reached clinical “maturity”.
The limitations of Isles of Langherans transplantation in the treatment of diabetes 1
Although recognized today as an option in the standard of care, in scientific terms the transplantation of islets of Langerhans is now considered “vintage” in the panorama of cellular therapies for the treatment of diabetes. The advancement of knowledge in the field of biology, tissue bioengineering associated with the possibility of shaping the cellular expression of genes, now proposes approaches capable of overcoming the current limitations of islet transplantation, including the reduced availability of organs. and the need to use accompanying immunosuppressive therapy.
The future of cell therapies for insulin production
Several laboratories in recent years have developed protocols for the differentiation of pluripotent stem cells into islets of Langerhans and a great effort in recent years has focused on the development of cell products with a good safety profile that allows their clinical application. In fact, it is possible in a time of 2-3 weeks to retrace the steps that normally govern the organogenesis of the pancreas during the nine months of fetal life in the laboratory.
The availability of this new generation of insulin-producing cells allowed the development of the first studies in humans. Currently, 6 clinical trials are registered worldwide using human pluripotent stem cell-derived cells for the treatment of type 1 diabetes and the first patients in which they were implanted showed clear clinical benefit.
Cell engineering
We have therefore ‘learned’ to produce insulin-producing cells in the laboratory and therefore in the future we may no longer need to resort to organ donors; Moreover, from these first studies in humans, proofs of principle have been obtained that these cells are able to function to the point of making the subject insulin independent.
More knowledge will need to be gained before these approaches can be extended to a large scale, but previous experience with transplanting the islets of Langerhans will allow the field to develop more quickly. The most important bet in the near future is to be able to use these cells without the need for immunosuppressive therapy.
In this regard, various avenues are being explored, such as inserting cells inside a ‘container’ that isolates them and protects them from attack by the immune system or genetically modifying them by silencing some genes and inserting others that make them invisible to the immune system. Achieving this goal would open up the possibility of widespread use for the treatment of type 1 diabetes and a portion of individuals with type 2 diabetes.
Translational research
In this panorama, the importance of integration between research and clinic is increasingly evident. It is therefore desirable that the most advanced centers in our country develop, perhaps based on the consolidated experience of transplant medicine, multidisciplinary clinical units, dedicated to regenerative medicine, capable of implementing the “from bench to bed” approach and also deal with the organizational and regulatory aspects by putting in place new management models which today constitute a critical element for the possibility of extending innovation to numerous pathologies potentially curable with regenerative medicine approaches.
Professor Lorenzo Piemonti is director of the Regenerative and Transplant Medicine Unit and the Diabetes Research Institute of the IRCCS San Raffaele Hospital