Scientists develop method for generating novel stem cells
Hospital-acquired infections that are resistant to traditional antibiotic treatment have become increasingly common in recent years, confounding health care professionals and killing thousands of Americans. Now, in studies that could lead to new ways to prevent this growing public health danger, a team of University of Cincinnati (UC) researchers is exploring a “zinc zipper” that
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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.
The issue is that pluripotent stem cells can be represented by cells from two distinct stages of embryonic development - the early pre-implantation blastocyst stage and the later post-implantation epiblast stage. Today, conventional mouse embryonic stem cells represent the pre- implantation stage pluripotent cells, and human embryonic stem cells appear to represent later post- implantation stage pluripotent cells.
Early- and late-stage cells have very different properties. For example, they respond differently to the same signals given to stem cells to differentiate into specific types of cells. The pre-implantation stage of cells will differentiate into one type of cell, while post-implantation stage of cells will turn into other types of cells. Their propensity toward specific cell types and growth properties are also different. The novel human pluripotent cells created by the scientists appear to represent the early stage of pluripotent cells - closer to well researched conventional mouse embryonic stem cells - and grow with better properties.
“The different behaviors of the pre- and post-implantation pluripotent stem cells means that findings from research done on mouse embryonic stem cells are often not translatable to work done on human embryonic stem cells,” Ding says. “With our new human pluripotent stem cells, we again have proof of principle that human stem cells can be created that are similar to mouse embryonic stem cells. The knowledge gained from mouse studies, therefore, will be more directly translatable to human cells, offering an advantage in biomedical research.”
Researchers have identified a stage during dopamine neuron differentiation that may be an ideal time to collect human embryonic stem cells for transplantation to treat Parkinson’s disease, according to data presented at Neuroscience 2008, the 38th annual meeting of the Society for Neuroscience. Lorraine Iacovitti, Ph.D., professor and interim director of the Farber Institute for
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Scientists at the Stanford University School of Medicine and at UC-San Francisco have succeeded in isolating stem cells from human testes. The cells bear a striking resemblance to embryonic stem cells - they can differentiate into each of the three main types of tissues of the body - but the researchers caution against viewing them
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Stem Cell Sciences plc has announced that pioneering research describing a technique for creating authentic embryonic stem (ES) cells from rats has been published in the prestigious peer-reviewed journal, Cell. This publication is believed to be the first in which germ-line transmission from rat ES cells has been definitively demonstrated. It uses technology licensed exclusively
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Stem cell researchers at UCLA have proven definitively that blood stem cells are made during mid-gestational embryonic development by endothelial cells, the cells that line the inside of blood vessels. While the anatomic location in the embryo where blood stem cells originate has been well documented, the cell type from which they spring was less
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Experiments at Johns Hopkins have found that the gradual maturing of embryonic cells into cells as varied as brain, liver and immune system cells is apparently due to the shut off of several genes at once rather than in individual smatterings as previous studies have implied. Working with mouse brain and liver cells, as well
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