Highlights of Stem Cell Research
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2008 Articles
- Neurons from Reprogrammed Adult Mouse Skin Cells Improve Symptoms in Rat Model of Parkinson's Disease
Scientists hope one day to replace the dopamine-producing nerve cells (neurons) lost in Parkinson's Disease with neurons derived from stem cells. Previously, scientists coaxed human embryonic stem cells (hESCs) into becoming dopamine-producing neurons. Another team of scientists now report generating dopamine-producing neurons from mouse-induced pluripotent stem cells (iPSCs). They tested the function of their derived dopamine-producing neurons by injecting them into the brains of rats used as a model for Parkinson's disease. Treated rats showed improvement in their Parkinsonian symptoms. These results demonstrate that animal iPSCs are capable of replacing lost cells and improving disease in animal models. They also offer hope that human iPSCs may one day enable scientists to develop patient-specific cells for replacing those lost or damaged by disease. Proceedings of the National Academy of Sciences of the USA 105(15):5856–5861, laboratory of R. Jaenisch. 2008 April 15.
- What Molecular Changes Enable Reprogramming?
Scientists have successfully reprogrammed adult mouse and human cells to behave like embryonic stem cells (ESCs). These reprogrammed adult cells are known as induced pluripotent stem cells, or iPS cells. Although iPS cells share many characteristics of ESCs, scientists have not yet identified what molecular changes enable reprogramming. To address these questions, NIH-funded scientists developed a special virus that allowed them to start and stop the expression of genes used in reprogramming (Oct4, Sox2, c-Myc, and Klf4) at will. Using their new "on/off switch," they determined the minimum amount of time that an adult cell must be exposed to these gene products in order to be reprogrammed. They also identified specific events, such as changes in level of gene expression or gene activation versus inactivation, that are indicative of cells at different stages of the reprogramming process. Scientists can now use this information to sort cells that are reprogrammed from those that are not. They will also be able to use what they know about the stages of reprogramming and exposure time as they develop new reprogramming techniques that eliminate the potential cancer risks of the viruses and genes used in the current methods. Cell Stem Cell 2(3):230–240, laboratory of K. Hochedlinger. 2008 March 6.
- Human Embryonic Stem Cell-Derived Neurons Treat Stroke in Rats
Scientists hope to use embryonic stem cells to generate neurons to replace those lost to disease, including the loss of nerve cells (neurons) in the brain that happens after a stroke. Scientists can already drive human embryonic stem cells (hESCs) into becoming neurons. However, transplants of these cells into animal models of human diseases sometimes "overgrow" and form tumors, suggesting that the transplants contain both desirable neurons and undesirable undifferentiated cells. NIH-funded scientists now report developing a cell culturing method that selects only human neural stem cells (hNSCs), and then drives them to become mature neurons, with no undifferentiated cells remaining. Transplants of these cells into rats did not produce any tumors, at least within the 2 month period of observation. In addition, rats that had suffered a stroke and subsequently stopped using one front paw began using that paw again after receiving transplanted human neurons. Post-mortem tissue sections of the treated rats' brains showed transplanted human neurons grew towards the site of neuron loss and did not appear to generate any tumors. The scientists now hope to study these hESC-derived neurons to learn how they differentiate and how they are different from human neurons derived from other culturing methods or tissue sources. Scientists also hope to adapt this technique to treat human stroke patients. PLOS One 3(2): e1644, laboratory of G.K. Steinberg. 2008 February 20.
- Muscular Dystrophy in Mice Treated with Muscle from Mouse Embryonic Stem Cells
Muscular dystrophy (MD) is an inherited disease characterized by progressive weakness and degeneration of the skeletal muscles that control movement. Current treatments for MD aim to slow the disease's progression but can't cure it or completely halt its progression. One possible hope lies in replacing diseased muscles with new muscle cells, generated from embryonic stem cells (ESCs). However, scientists have had difficulty generating skeletal muscle from ESCs, due in part to a lack of useful ways to identify developing skeletal muscle amidst other cell types. Privately funded scientists have now developed such a method in mice, as well as another method to sort muscle cells from undifferentiated stem cells that could divide uncontrollably and produce tumors after transplantation. The scientists injected the mouse ESC–derived skeletal muscle cells into mice with an MD-like muscle-wasting condition. Tests showed that treated mice's muscles had an improved ability to contract, and treated mice fared better than untreated diseased mice on standard tests for muscle function. In the future, scientists hope to test the ability of human embryonic stem cell (hESC)–derived muscle cells to treat human MD. Nature advance online publication, laboratory of R.C.R. Perlingeiro. 2008 Jan 20.
- Single Cell Biopsy Successfully Generates Human Embryonic Stem Cell Line; Biopsied Embryos Develop to Blastocyst Stage
In 2006, privately funded scientists successfully established human embryonic stem cell (hESC) lines using cells taken from pre-implantation human embryos (see Scientists Generate Human Embryonic Stem Cell Lines from Single Cells). However, the previous method involved dissociation of the embryos (i.e., the embryos were destroyed) and co-culture with existing hESCs. In this latest publication from the same laboratory, the scientists removed only one or two cells from each embryo via a biopsy procedure. These one or two cells were used to generate hESC lines. At the same time, the scientists cultured the biopsied embryos to the blastocyst stage and then froze them. One of the cell lines developed was cultured with a protein called laminin instead of being cultured with existing hESCs. However, ethical considerations make it uncertain whether scientists will ever test if the cells remaining after removal of a single cell can develop into a human being, at least in embryos that are not at risk for carrying a genetic disorder. Cell Stem Cell doi:10.1016/j.stem.2007.12.013, laboratory of R. Lanza. 2008 Jan 10.
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