Cell Therapy for Diabetes

Fri14  Oct11:00am(30 mins)
 Kevin Docherty


Cell therapy
in the form of human islet transplantation has been a successful form of
treatment for patients with type 1 diabetes for over 15 years, but is
significantly limited by lack of suitable donor material. During the islet
isolation procedure, 98% of the pancreas, comprising acinar and ductal tissue
(the exocrine tissue) is normally discarded. The aim of this study was to
optimize a protocol whereby this exocrine material could be efficiently
reprogrammed to provide an additional supply of islets for transplantation. On
arrival in the lab the exocrine-enriched fraction was immediately plated on to
tissue culture dishes. The cells attached to the dish and formed a monolayer,
which if left unchecked would undergo the epithelial to mesenchymal transition
(EMT). Reprogramming was initiated by treatment with adenoviruses containing
the pancreatic transcription factors Pdx1, MafA, Ngn3 and Pax4. Four days later
(D4) the cells were treated with an siRNA to inhibit expression of the endogenous
transcription factor ARX. The protocol was complete by D10. The reprogrammed
cells share many of the properties of adult endogenous Beta cells and compare well
with surrogate Beta cells generated from human embryonic stem or iPS cells.   We estimate that around 1.5 x 108
reprogrammed cells would have a therapeutic effect if transplanted in human
diabetics; thus one recipient pancreas could provide numerous islet grafts.

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