New Insights into Diabetes Cell Therapy.

Abstract

Since insulin discovery, islet transplantation was the first protocol to show the possibility to cure patients with type 1 diabetes using low-risk procedures. The scarcity of pancreas donors triggered a burst of studies focused on the production of new β cells in vitro. These were rapidly dominated by pluripotent stem cells (PSCs) demonstrating diabetes-reversal potential in diabetic mice. Subsequent enthusiasm fostered a clinical trial with immunoisolated embryonic-derived pancreatic progenitors. Yet safety is the Achilles' heel of PSCs, and a whole branch of β cell engineering medicine focuses on transdifferentiation of adult pancreatic cells. New data showed the possibility to chemically stimulate acinar or α cells to undergo β cell neogenesis and provide opportunities to intervene in situ without the need for a transplant, at least after weighing benefits against systemic adverse effects. The current studies suggested the pancreas as a reservoir of facultative progenitors (e.g., in the duct lining) could be exploited ex vivo for expansion and β cell differentiation in timely fashion and without the hurdles of PSC use. Diabetes cell therapy is thus a growing field not only with great potential but also with many pitfalls to overcome for becoming fully envisioned as a competitor to the current treatment standards.