Chapter 6 - Pluripotent Stem Cell–Derived Islet Replacement Therapy for Diabetes

Abstract

Cell replacement therapy for type 1 diabetes (T1D) is in many ways an ideal first product concept for the emerging field of regenerative medicine to pursue. The unmet medical need is great, the lost or damaged cells are well-defined and, as they are endocrine cells, the replacement cells do not necessarily have to be integrated in an anatomically specific fashion. Further, the concept of islet cell replacement has been validated by way of the well-established efficacy of cadaver islet transplants in T1D patients. Human pluripotent stem cells represent an excellent source material for the manufacture of replacement cells because (1) they can be propagated virtually indefinitely and (2) through a directed differentiation process they can be converted into any cell type in the body, including pancreatic progenitor cells. Pancreatic progenitor cells have the potential to produce the full complement of pancreatic endocrine cells, including glucose-responsive insulin-secreting beta cells, following implant. These cells, although human in origin, are not derived from the recipients and therefore require protection from the immune system to engraft, mature and function. This protection can potentially be accomplished in various ways, including immune suppression or encapsulation. Encapsulation is an attractive option as it would avoid the potential treatment-associated health risks of immune suppression; however, encapsulation is not without its own challenges. Amongst encapsulation concepts, macroencapsulation may have certain advantages over microencapsulation strategies. In 2014, for the first time, a clinical trial investigating a macroencapsulated, pluripotent stem cell-derived, islet replacement cell therapy for T1D was launched. While results from this and subsequent clinical trials will unfold in the coming years, we also look forward to new technologies that may further advance the implementation of cell replacement therapy for diabetes.