The journey of islet cell transplantation and future development

Abstract

Intraportal islet transplantation has proven to be efficacious in preventing severe hypoglycemia and restoring insulin independence in selected patients with type 1 diabetes. Multiple islet infusions are often required to achieve and maintain insulin independence. Many challenges remain in clinical islet transplantation, including substantial islet cell loss early and late after islet infusion. Contributions to graft loss include the instant blood-mediated inflammatory reaction, potent host auto- and alloimmune responses, and beta cell toxicity from immunosuppressive agents. Protective strategies are being tested to circumvent several of these events including exploration of alternative transplantation sites, stem cell-derived insulin producing cell therapies, co-transplantation with mesenchymal stem cells or exploration of novel immune protective agents. Herein, we provide a brief introduction and history of islet cell transplantation, limitations associated with this procedure and methods to alleviate islet cell loss as a means to improve engraftment outcomes.

Chemical Strategies for Improving Islet Transplant Outcomes

“…ALL of the approaches described in this review address important aspects of this challenging problem, and as the field evolves there will likely be multiple solutions that incorporate new discoveries coupled with previously described interventions. A recent review by leaders in the field delivers a similar perspective, highlighting the need to address neovascularization, inflammation and oxidative stress, to explore alternative cell sources, to embrace advances in microencapsulation devices, and to adopt effective strategies from recent developments in immune regulation [243].…”

Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction

“…Several cellular structures have been reported to act as mechanosensors, and are all expressed in β-cells: protein complexes of cell-ECM and cell-cell adhesions [60,79], primary cilia [78], stretch-activated ion channels [80], glycocalyx [81], G-protein coupled receptors [75], and growth factors receptors [82] (Figure 2A). Cells 2020, 9,413 7 of 23…”

Using GRGDSPC peptides to improve re‐endothelialization of decellularized pancreatic scaffolds

“…4,5 Unfortunately, the application of this procedure is limited by the large numbers of patients, shortage of suitable pancreases, and the requirement of life-long immunosuppressant drugs. 6 Clearly, replacement with functional pancreatic tissue should be proposed as a regenerative therapy that could restore the physiological regulation of the blood sugar level. Over the past decade, the fields of regenerative medicine and tissue engineering have offered new strategies for the generation of an insulin-secreting organ.…”

“…Islet or pancreas transplantation represents the only curative treatment for end‐stage diabetes . Unfortunately, the application of this procedure is limited by the large numbers of patients, shortage of suitable pancreases, and the requirement of life‐long immunosuppressant drugs . Clearly, replacement with functional pancreatic tissue should be proposed as a regenerative therapy that could restore the physiological regulation of the blood sugar level.…”