Transplantation of insulin-producing pancreatic beta-cells shows great promise as a treatment for type 1 diabetes, but development of this therapy is hampered by a severe shortage of donor beta-cells, which are obtained from deceased human donors. In October's Nature Biotechnology, Kobayashi, Yoon and colleagues describe a 'reversibly immortalized' cell line that can supply large amounts of insulin-producing human beta-cells. Ultimately, a cell line of this sort may provide an abundant source of beta-cells for transplantation and an alternative to beta-cells from cadavers.
Type 1 diabetes results from the loss of insulin-producing beta-cells in the pancreas. Because the supply of beta-cells from cadavers is insufficient to meet the needs of 99% of diabetic patients, alternative sources of beta-cells would be highly desirable. Previous efforts to coax mature human beta-cells to survive and replicate in the laboratory have not succeeded, however, because the cells died or lost their ability to produce insulin in response to sugar stimulation.
Kobayashi, Yoon and colleagues got around this problem by manipulating and analyzing large numbers of human beta-cells. First, they added genes that extend cell lifespan to human beta-cells and looked for the rare cells that did not form tumors and that expressed insulin and other beta-cell proteins. Out of over 250 cell lines screened, only one passed this test. This cell line was allowed to replicate to produce large numbers of cells. Then, the genes that extend cell lifespan were removed to ensure that the cells would not form tumors and to promote beta-cell behavior. The resulting cells produced about 40% as much insulin as normal beta-cells and successfully controlled blood sugar levels in diabetic mice for over 30 weeks.
Further research is needed before these cells can be considered for testing in humans.
Ji-Won Yoon (Chicago Medical School, North Chicago, IL, USA)
Additional contact for comment on paper:
Christopher Newgard (Duke University Medical Center, Durham, NC, USA)
Abstract available online.
(C) Nature Biotechnology press release.
Message posted by: Trevor M. D'Souza
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