*Molecular Challenges and Advances in Clinical Islet Transplantation DOI: http://dx.doi.org/10.5772/intechopen.108571*

observed in only 12.4 percent for periods of more than 1 week, and merely 8.2 percent could sustain the beneficial outcome for more than a year. Predominantly in these procedures the immunosuppression regimen comprised of antibody induction with an antilymphocyte globulin combined with cyclosporine, azathioprine, and glucocorticoids. Many of these immunosuppression regimens pose a threat of damaging beta cells or induce peripheral insulin resistance. Immunosuppressive drugs that concentrate in the liver can be toxic to the islets, yet must be taken for the lifetime of the graft. Currently, we are stepping into an era of accessing new and more potent immunosuppressive agents that will provide greater immunologic protection without diabetogenic side effects. Such an approach is glucocorticoid-free immunosuppressive protocol that includes sirolimus, low-dose tacrolimus, and a monoclonal antibody against the interleukin-2 receptor (daclizumab) for use in a trial of islet transplantation alone for patients with brittle type 1 diabetes. This has shown to result in insulin independence with excellent metabolic control when glucocorticoid-free immunosuppression is combined with the infusion of an adequate islet mass. Additionally, this immunosuppressive protocol has not clinically evidenced any episodes of graft rejection, and it appears to be effective in preventing autoimmune recurrence of diabetes [67].

Islet transplantation has emerged as a promising treatment option for type 1 diabetes. Still its progress is challenged by barriers like patient accessibility and longterm graft function. These can be overcome by amalgamating emerging technologies in biomaterials with drug delivery and immunomodulation. The hepatic microenvironment and traditional systemic immunosuppression can stress the vulnerable islets and limit the success rate of transplantation [68].

2.Other challenges like limitation in islet engraftment and function, low oxygen tension, insulin-induced hepatic steatosis, lipotoxicity and inflammation

Intrahepatic transplantation is a minimally invasive portal infusion that results in islet entrapment within hepatic sinusoids. The islet engraftment and function is restrained by hepatic portal vasculature. An instant blood-mediated inflammatory reaction (IBMIR) is a resultant of vascular delivery. Also noticed are activated complement and coagulation cascades, and leucocyte infiltration leading to the loss of nearly two-thirds of the islets within the first few days after transplantation. Islets that survive inside the hepatic portal environment experience high glucose levels, low oxygen tension, and first-pass exposure to metabolites and pharmaceuticals. Intrahepatically transplanted islets may also be lost as a result of localized, insulininduced hepatic steatosis, lipotoxicity and inflammation. A transformative approach to islet transplantation may be achieved through the adaptation of technologies for locally controlling the transplant microenvironment to promote engraftment and long-term function while minimizing or eliminating systemic non-specific immunosuppression with local immunomodulation or operational tolerance induction [68].

Resolving approaches

• Natural or synthetic biomaterials can be employed to engineer an extrahepatic space to localize islets and control the microenvironment after transplantation. Transplantation at extrahepatic and extravascular site is enabled through the support of biomaterial scaffold, which proves beneficial by avoiding the unfavorable influences on the liver environment and the IBMIR. Interestingly, the extrahepatically implanted biomaterial scaffolds can be retrieved, facilitating the adoption of insulin-producing cells derived from stem cells.

