Using the liver to make the pancreas

Who would guess that it kind of makes sense to use the liver to produce beta cells, the vehicles for easing the problem of type 1 diabetes? Well, I was convinced of just that during a talk I attended yesterday at this year?s linkurl:Keystone meeting;http://www.keystonesymposia.org/Meetings/ViewMeetings.cfm?MeetingID=786 on stem cell biology. linkurl:Jonathan M.W. Slack;http://www.bath.ac.uk/bio-sci/slack.htm of the University of Bath in the UK and his colleagues have been studying the use of liver cells to produce beta cells -- an admittedly "bizarre choice," he said, given that the adult liver and pancreas are quite different. However, from a developmental biology point of view, the organs are closely related, and one signal, FGF, appears to distinguish one from the other in a mouse embryo. A series of experiments appeared to suggest that it might be possible to convert liver cells into pancreas cells using Pdx-1, which is essential for the formation of the pancreas. The researchers administered Pdx-1 to mice, and discovered little clusters in the liver that looked like beta cells, at which point they "got very excited," Slack said. However, they soon found similar clusters in the biliary system of untreated mice, which made things even more exciting -- it presented what they believe is the first evidence that mice may carry naturally-occurring beta cells outside of the pancreas. The newly-discovered cells have C-peptide, and electron microscopy showed they have secretory granules with a pale halo -- all hallmarks of beta cells. To make sure that the cells indeed came from the liver, and didn?t simply migrate from the pancreas, the authors performed a labeling experiment, and found that the frequency of labeling in the supposed beta cells matched the frequency of labeling in the biliary system, not in the pancreas. Slack explained that he and his colleagues suspect these cells -- just few in number -- stem from "misexpression" of transcription factors during development. The findings suggest that biliary epithelium may be another target for producing excess beta cells, Slack noted. For instance, although it would be a "nightmare" from a regulatory standpoint, he said researchers could use a protein or RNA-delivery system to reprogram a small number of liver cells to produce insulin in adult patients. The reality of this is a long way off, but Slack?s point is valid. When creating new tissue, why limit yourself to building blocks from the organ you?re trying to heal?

Using the liver to make the pancreas

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