The study, which appears in the December 18 online version of Cell Stem Cell and the January 2009 print edition of the journal, provides proof of principle that alternative sources of stem cells can be created.
The team, which included scientists from Scripps Research, Peking University, and the University of California, San Diego, conducted the studies to establish novel rat induced pluripotent stem cell lines (riPSCs) and human induced pluripotent stem cell lines (hiPSCs) by using a specific cocktail of chemicals combined with genetic reprogramming, a process whereby an adult cell is returned to its early embryonic state. Pluripotency refers to the ability of a cell to develop into each of the more than 200 cell types of the adult body.
Mimicking Human Physiology
Scientists genetically engineer embryonic stem cells to create mouse models that contain the engineered genes - so-called transgenic animals - in the hope of applying the knowledge gained from studying such mice to benefit humans. Although using mouse pluripotent embryonic stem cells has been the standard since these cells were first derived in 1981, researchers have long wanted to apply such powerful techniques to other animal species to help the study of human physiology and disease.
The major advantage of using other animal species, such as rats, is that the physiology of these animals can better mimic human physiology, for example, in studies of metabolic and neurological diseases. The size of other animals also is an advantage because larger organs and tissues are easier to work with. Because of these benefits, scientists have created transgenic animals from species other than mice, but the lack of pluripotent stem cells from these species and the tedious and imprecise techniques currently available has made the process difficult.
"Mouse models created with pluripotent embryonic stem cells are wonderful tools for understanding the fundamental biology of genes," says Sheng Ding, Ph.D., an associate professor in the Scripps Research Department of Chemistry who was senior author of the study with Peking University investigator Hongkui Deng, Ph.D. "But in some important ways these models are less than ideal. Our demonstrated technologies will enable unprecedented and broad applications for better creating animal models from other species."
Novel and More Robust Human Pluripotent Stem Cells
In another closely related aspect of this work, Ding has also shown that a new kind of human pluripotent stem cell can now be created using the same chemical and reprogramming methods used to create the rat pluripotent stem cells. Human pluripotent stem cells hold promise for modeling human development and disease, testing drugs, and providing unlimited functional cells for cell replacement therapy.
"Recent studies have found, however, that conventional human embryonic stem cells represent a different pluripotent cell type and are not the counterpart of the conventional, and most useful, mouse embryonic stem cells," Ding says.