Developing Stem Cell Therapy for Type 1 Diabetes Mellitus

The restricted availability of cadaveric isolated human donor islets sharply limits progress in clinical trials of islet cell transplantation. Furthermore, the host's general pharmacologic immunosuppression is invariably needed to grant survival and function of the human islet grafts. The former mandates validation of new sources of insulin producing cells. The latter requires new strategies to circumvent use of general immunosuppressive agents. A possible solution to these problems could consist using of human stem cells, whose availability is indefinite, that are suitable for both, differentiation into endocrine cell phenotypes, and genetic manipulations to alter immunogenicity. Pluripotent human stem cells, either embryonic (ESCs), derived from the blastocyst, or those originating from adult somatic cells, artificially induced to pluripotency (iPSCs), or finally, multipotent human adult mesenchymal stem cells (MSCs) may be considered. MSCs are more difficult to trans-differentiate into Beta-like cells, but they hold powerful immunoregulatory properties, and do not pose ethical problems. Both ESCs and iPSCs show pro's and con's, in terms of ethical acceptance (ESCs), and technical feasibility (iPSCs), with the pending immune problems, that might be attenuated by gene editing manoeuvres to render the cells ‘immune evasive’. Early pilot clinical trials with either ESCs or iPSCs in immunosuppressed T1D patients showed that hyperglycemia can be reversed, although challenges remain.