Embryonic Stem Cell Study Replicates Adult Stem Cell Advances Achieved Over a Year Ago

Date: 04/27/2001

A report in today’s issue of Science magazine reports on one of the very few successes scientists have achieved using embryonic stem (ES) cells: the apparent conversion of such cells into insulin producing pancreatic islet cells. The mouse embryonic stem cell work merely replicates an advance made with adult stem cells over a year ago.

However, the mouse embryonic stem cells secreted only 1/50th the normal amount of insulin, and diabetic mice implanted with the cells still died. In contrast, scientists using adult stem cells achieved full insulin expression from their differentiated adult stem cells, including full ability to protect from diabetes once transplanted back into the mice:

  • In March, 2000, researchers at the University of Florida announced that they had reversed diabetes in mice using adult 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 survive without further need for insulin shots (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).

Moreover, in July and October, 2000, scientists identified human adult pancreatic stem cells.

In contrast, human ES cells have yet to be shown to undergo differentiation to insulin-secreting cells:

  • Scientists at Harvard Medical School 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” (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).
  • Researchers in France 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 (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).

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.” (P. Serup et al., “Islet and stem cell transplantation for treating diabetes”; British Medical Journal 322, 29-32; 6 Jan 2001).

Late last year, Science magazine reported that genetic engineering of other adult body cells to release insulin upon feeding could be a treatment for patients with diabetes. A collaboration among scientists in Tennessee, Boston, and Alberta (Canada), developed a mouse cell line that could be induced to produce human insulin. Mice expressing the gene produced human insulin specifically in their gut cells. This insulin protected the mice from developing diabetes and maintained glucose levels even after destruction of the native insulin-producing cells in their pancreas (A.T. Cheung et al.; “Glucose-dependent insulin release from genetically engineered K cells”; Science 290, 1959-1962; Dec 8 2000).

Adult stem cells have already been used successfully in clinical trials to treat cartilage defect in children, restore vision to patients who were legally blind, relieve systemic lupus, multiple sclerosis, and rheumatoid arthritis and cure severe combined immunodeficiency disease.

For further information on current clinical and potential applications of adult stem cells, please visit: www.stemcellresearch.org.

Experts on the science and ethics of stem cell research from Do No Harm: The Coalition of Americans for Research Ethics are available for comment. To speak with them, please contact Gene Tarne or Michelle Powers at 703-684-8352