Stem Cell Report – September/October 2000

Date: 11/02/2000

Embryonic stem cell development falls short of previous advance made with adult stem cells

Science magazine reports one of the few successes using embryonic stem cells: the apparent conversion of mouse embryonic stem cells into insulin producing pancreatic islet cells. This work replicates developments achieved with adult stem cells more than a year ago (see following item).

The mouse embryonic stem cells secreted only 1/50th the normal amount of insulin, and diabetic mice receiving the implanted cells still died. This contrasts with last year’s adult stem cell advance, in which scientists achieved full insulin expression from the differentiated adult stem cells, including full ability to protect from diabetes once transplanted back into the mice.1

Adult stem cells reverse diabetes in mice

Researchers at the University of Florida announced in March 2000 that they have reversed diabetes in mice using adult pancreatic stem cells. The pancreatic stem cells were harvested from adult donors and grown in culture, where they formed small functional organs known as islets of Langerhans (the insulin-secreting parts of the pancreas.) The cells were then injected under the skin of the diabetic mice, where they began secreting insulin. Within 7-10 days, the mice were able to regulate the levels of glucose in their blood and survived without further need of insulin shots.2

Scientists identify human adult pancreatic stem cells

Although human embryonic stem cells have yet to be shown to undergo differentiation to insulin secreting cells, scientists at Harvard Medical School have cultured human pancreatic ductal cells under specific conditions, inducing the cells to form islet buds and secrete insulin. “Thus, duct tissue from human pancreas can be expanded in culture and then be directed to differentiate into glucose responsive islet tissue in vitro. This approach may provide a potential new source of pancreatic islet cells for transplantation.”

In addition, researchers in France have found further evidence for pancreatic stem cells in humans. The pancreatic cells from healthy donors, when placed into culture, proliferated and expressed characteristics critical for production and secretion of insulin. The results are another step toward treatment of diabetes using adult stem cells.3

Comprehensive review finds adult stem cells present fewer biological problems for producing insulin secreting pancreatic beta cells

A recent comprehensive review in the British Medical Journal of possible stem cell treatments for diabetes noted that “Human pancreatic duct cells have also been grown successfully in vitro and induced to differentiate”, and “Not only does the use of adult donor ductal cells avoid the controversy of using fetal cells but there are fewer biological problems associated with making beta cells from duct cells than from, for example, embryonic stem cells.”

The authors also point out that insulin producing cells had been derived from mouse embryonic stem cells, but “this procedure gives rise to proliferating cells, and thereby potentially malignant cells, rather than mature, post-mitotic cells.”

The authors also note: “When the nature of pancreatic beta cell ontogeny is fully understood we may be able to mimic this process in vitro to propagate beta cells — either starting with duct cells derived from pancreatic donor specimens or by the use of other appropriate human stem cells (such as from bone marrow or even blood samples). This development would clearly be welcome because it would avoid the need for therapeutic cloning, with all the attendant controversy of creating human embryos solely for medical use.”

The authors conclude: “Of the techniques described above, the most promising is generation of beta cells from pancreatic duct cells. It is inherently a shorter biological step to make a beta cell from a duct cell than it is from other possible cells, such as embryonic stem cells and haemopoietic stem cells.”4

  1. N. Lumelsky et al., “Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets,” Sciencexpress, www.sciencexpress.org; Published online 26 April 2001; G. Vogel, “Stem Cells Are Coaxed to Produce Insulin,” Science 292, 615-617; 27 April 2001; V. K. Ramiya, et al, “Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells,” Nature Medicine6, 278-282, March 2000.
  2. V. K. Ramiya, et al, “Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells,” Nature Medicine 6, 278-282, March 2000.
  3. S. Bonner-Weir et al. “In vitro cultivation of human islets from expanded ductal tissue,” Proc Natl Acad Sci USA 97, 7999-8004; July 5, 2000; V. Gmyr et al., “Adult human cytokeratin 19-positive cells reexpress insulin promoter factor 1 in vitro: Further evidence for pluripotent pancreatic stem cells in humans,” Diabetes 49, 1671-1680; Oct. 2000.
  4. P. Serup et al., “Islet and stem cell transplantation for treating diabetes,” British Medical Journal 322, 29-32; 6 Jan 2001.
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