Generation of glucose-sensitive insulin-secreting beta-like cells from human embryonic stem cells by incorporating a synthetic lineage-control network

Easily and efficiently converting stem cells into insulin-producing cells would be the holy grail for patients suffering from type-1 diabetes, which don’t produce enough insulin to regulate their blood glucose levels. One way how this is currently attempted is the well-timed addition of chemicals and growth factors which trigger the signaling pathways necessary to differentiate stem cells into cells resembling insulin-producing beta cells. Yet the efficiency of this process as well as the functionality of the produced beta cells are severely limited. This is for instance due to the fact that every single cell might respond slightly different to the procedure and may not be ready yet when the next round of chemicals is added.

One advantage of synthetic biology is that we can design gene circuits which nearly autonomously regulate the differentiation process at a single cell level and don’t allow for an accumulation of overly heterogenous cells. In a publication in the Journal of Biotechnology we converted embryonic stem cells into glucose-responsive, insulin-producing beta cells by equipping them with a gene circuit that is regulated by a single chemical (vanillic acid). Thereby, we achieved higher efficiency as well as functionality of the resulting beta cells and hopefully bring the approach of stem cell-generated beta cells one step closer toward the clinics.

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