Vijayakumar K. Ramiya [1], Michael Maraist [1], Karl E. Arfors [2], Desmond A. Schatz [3], Ammon B. Peck [1, 4], and Janet G. Cornelius [4], "Reversal of Insulin-Dependent Diabetes Using Islets Generated in vitro from Pancreatic Stem Cells," Nature Medicine , Vol. 6, No. 3, pp. 278 - 282 (March 2000).
Ductal structures of the adult pancreas contain stem cells that differentiate into Islets of Langerhans. Here, we grew pancreatic ductal epithelial cells isolated from pre-diabetic adult non-obese diabetic mice in long-term cultures, where they were induced to produce functioning islets containing alpha, beta, and delta cells. These in vitro-generated islets showed temporal changes in mRNA transcripts for islet cell-associated differentiation markers, responded in vitro to glucose challenge, and reversed insulin-dependent diabetes after being implanted into diabetic non-obese diabetic mice. The ability to control growth and differentiation of islet stem cells provides an abundant islet source for beta-cell reconstitution in Type I diabetes.
1. Ixion Biotechnology, 13709 Progress Blvd., Box 13, Alachua, Florida 32615, USA
2. Q-Med of Scandinavia, San Diego, California, USA
3. Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida 32610, USA
4. Department of Pathology, Immunology & Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida 32610, USA
Correspondence should be addressed to A B Peck. E-mail: peck.pathology@mail.health.ufl.edu.
Diabetes Reversed in Mice
10:02 AM EST; February 29, 2000; New York, NY (AP) -- Scientists have reversed diabetes in mice by generating insulin-producing cells in a laboratory and transplanting them into the animals, an indication of how useful so-called stem cells might be. The mice had a version of Type 1 diabetes, which occurs when the body mistakenly destroys insulin-producing cells in the pancreas. People with this disease must inject themselves with insulin daily to survive.
Patients have been treated with transplants of islets, the insulin factories of the pancreas. But the success rate has been low, apparently in part because it's hard to get enough islets from a cadaver's pancreas. The new work suggests a way to overcome that problem: prodding immature stem cells from the pancreas to make abundant quantities of islets in the laboratory.
The mouse study by researchers at the University of Florida College of Medicine and elsewhere is reported in the March issue of the journal Nature Medicine. In one set of experiments, eight diabetic mice received the lab-generated islets and then were weaned from insulin injections over a few days. Within a week after injections stopped, they showed a decline in blood-sugar levels. They remained healthy without insulin injections until they were killed for examination of the implant, a period of up to 55 days from implantation.