**10. Islet transplantation**

In addition to pancreas transplantation, β cell mass transfer may be performed through islet transplantation. This procedure consists of islet cell isolation from pancreas as potential donors using both mechanical and enzymatic digestion protocol, following which islets are separated using a Ricordi chamber [41]. Isolated islets are infused into recipient's portal vein, without the need for vascular and/or enteric anastomosis, reducing the surgical risks of the procedure.

The attractiveness of a minimally invasive procedure and the possibility of multiple infusions without the surgical risks associated with whole-organ pancreas transplantation have positioned islet cell transplantation as a promising treatment for patients with diabetes. Despite these advantages, islet transplantation presents two critical drawbacks when compared to whole-organ transplant. Islets obtained from a minimum of 2–3 pancreasas are often needed in order to achieve euglycemia [41], increasing organ demand, and risk of recipients' sensitization. Additionally, islets direct engraftment into a vascularized bed exposes β cells to platelets and lymphocytes. Instant blood-mediated inflammatory reaction (IBMIR) is a well characterized event associated with innate immune reaction and coagulation and complement activation following islet transplantation, leading up to 25% of total islet cell mass loss following vena cava infusion [42]. Moreover, it may increase the risk of rejection and reduces overall graft survival.

In early 2000, the Edmonton group published some promising results using an induction immunosuppression protocol [41]. By the end of 2015, over 15,000 procedures had been performed worldwide [5]. Reported 1- and 5-year insulin independence is up to 80 and 50%, respectively [5].

Novel biocompatible implantation devices and gene editing tools foresee a bright future for islet transplantation. 3D-bioprinting is being used to build an islet-blood interface which enables β cell survival and insulin production, while avoiding immune activation and graft rejection [43]. On the other hand, generation of human-induced pluripotent stem cells (hiP-SCs) has opened the door for personalized medicine and cell-based therapy. iPSCs can proliferate unlimitedly in culture and harbor the potential to generate all cell types in the adult body. Generation of hiIPSC-derived β cells has been published by several groups, using different protocol, with varying degrees of success [44, 45]. The advantage is the possibility to generate tailor-made islet cells, particularly β cells, from recipient-derived hiPSC, evading the risk of alo-rejection. One can envision in the near future hiPSC-derived cells implanted in a biocompatible device for the treatment of type 1 diabetic patient.

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For the time being, islet cell transplantation remains at an almost investigation level due to smaller insulin independence when compared to pancreas transplantation. Nonetheless, it is a suitable option for selected type 1 diabetic patients, and to those with a surgical contraindication for whole-organ transplantation. Finally, islet transplantation presents a promising future as the techinique of election for β cell mass transfer.
