“Latest Stem Cells News”

Mouse skin cells can be converted directly into cells that become the three main parts of the nervous system, according to researchers at the Stanford University School of Medicine. The finding is an extension of a previous study by the same group showing that mouse and human skin cells can be directly converted into functional neurons.

The multiple successes of the direct conversion method could refute the idea that pluripotency (a term that describes the ability of stem cells to become nearly any cell in the body) is necessary for a cell to transform from one cell type to another. Together, the results raise the possibility that embryonic stem cell research and another technique called “induced pluripotency” could be supplanted by a more direct way of generating specific types of cells for therapy or research.

This new study, published online Jan. 30 in the Proceedings of the National Academy of Sciences, is a substantial advance over the previous paper in that it transforms the skin cells into neural precursor cells, as opposed to neurons. While neural precursor cells can differentiate into neurons, they can also become the two other main cell types in the nervous system: astrocytes and oligodendrocytes. In addition to their greater versatility, the newly derived neural precursor cells offer another advantage over neurons because they can be cultivated to large numbers in the laboratory — a feature critical for their long-term usefulness in transplantation or drug screening.

In the study, the switch from skin to neural precursor cells occurred with high efficiency over a period of about three weeks after the addition of just three transcription factors. (In the previous study, a different combination of three transcription factors was used to generate mature neurons.) The finding implies that it may one day be possible to generate a variety of neural-system cells for transplantation that would perfectly match a human patient.

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Much to the dismay of patients and physicians, cancer stem cells — tiny powerhouses that generate and maintain tumor growth in many types of cancers — are relatively resistant to the ionizing radiation often used as therapy for these conditions. Part of the reason, say researchers at Stanford University School of Medicine, is the presence of a protective pathway meant to shield normal stem cells from DNA damage. When the researchers blocked this pathway, the cells became more susceptible to radiation.

“Our ultimate goal is to come up with a therapy that knocks out the cancer stem cells,” said Robert Cho, MD, a clinical instructor of pediatrics. “If you irradiate a tumor and kill a lot of it but leave the cancer stem cells behind, the tumor has the ability to grow back.” As a result, patients can relapse months or years after seemingly successful treatment.

Cho and radiation oncologist and post-doctoral fellow Maximilian Diehn, MD, PhD, are co-first authors of the research, which was published on Feb. 4 in Nature. They collaborated with scientists at Stanford and City of Hope National Medical Center to conduct the research. They studied breast epithelial stem cells from humans and mice to unravel why cancer stem cells are more resistant to radiation than other cancer cells.

“Since cancer stem cells appear to be responsible for driving and maintaining tumor growth in many tumors, it is critical to understand the mechanisms by which these cells resist commonly used therapies such as chemotherapy and radiotherapy,” said Diehn. “Ultimately, we hope to improve patient outcomes by developing therapeutic approaches that directly target cancer stem cells or that overcome their resistance mechanisms.”

The origin of cancer stem cells is still under debate. Some may arise from normal adult stem cells gone awry. Others may represent specialized cells from adult tissues that have acquired a stem-cell-like state through a series of mutations. What’s clear is that cancer stem cells can reconstitute an entire tumor cell population when transplanted into an immune-deficient animal, and destroying them is likely to be critical in order to stop the growth and spread of the disease.

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The addition of two particular gene snippets to a skin cell’s usual genetic material is enough to turn that cell into a fully functional neuron, report researchers from the Stanford University School of Medicine. The finding, published online July 13 in Nature, is one of just a few recent reports of ways to create human neurons in a lab dish.

The new capability to essentially grow neurons from scratch is a big step for neuroscience research, which has been stymied by the lack of human neurons for study. Unlike skin cells or blood cells, neurons are not something that’s easy for a living human to donate for research.

“A major problem in neurobiology has been the lack of a good human model,” said senior author Gerald Crabtree, MD, professor of pathology and of developmental biology. “Neurons aren’t like blood. They’re not something people want to give up.”

Generating neurons from easily accessible cells, such as skin cells, makes possible new ways to study neuronal development, model disease processes and test treatments.

It also helps advance the effort, still in its infancy, to replace damaged or dead neurons with new ones.

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Any legislation that slows human embryonic stem cell research is likely to also seriously harm the study of induced pluripotent stem cells, according to a new study by researchers at the Stanford University School of Medicine, the Mayo Clinic and the University of Michigan.

The finding strongly refutes the idea that embryonic stem cell research can be abandoned in favor of the less-controversial iPS cells, which are derived from adult human tissue.

“If federal funding stops for human embryonic stem cell research, it would have a serious negative impact on iPS cell research,” said Stanford bioethicist Christopher Scott, citing a “false dichotomy” between the cell types. “We may never be able to choose between iPS and ES cell research because we don’t know which type of cell will be best for eventual therapies.”

Scott, who directs Stanford’s Stem Cells in Society Program, is the first author of the study, which compared the patterns of scientific publication on human embryonic and induced pluripotent stem cells. The study was published in the June 10 issue of Cell.

The researchers also concluded that human embryonic stem cell research does not siphon federal funding away from studies of iPS cells, as has been claimed by the two plaintiffs in an ongoing Washington, D.C., district court case under consideration by Judge Royce Lamberth. Instead, studies of the two types of stem cells are likely to occur in tandem as established embryonic stem cell researchers rush to buffer themselves against a possible loss of federal funding.

“We’re finding that scientific decisions are being made not because of science, but in response to other constraints, such as which cell types qualify for federal funding, how many lines are available and which can be obtained quickly and easily,” said Scott.

As a result, the fields have become so tightly intertwined as to be inseparable; any loss of funding for these researchers will negatively impact all the work in their labs, including iPS cell research, Scott and his colleagues conclude.

Unlike embryonic stem cells, which are derived from human embryos, iPS cells can be created from adult tissue such as skin cells. They look and act like embryonic stem cells, but recent research has suggested that there are significant differences between the two cell types that may affect how they can be used for research and eventual human therapies.

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Even Superman needed to retire to a phone booth for a quick change. But now scientists at the Stanford University School of Medicine have succeeded in the ultimate switch: transforming mouse skin cells in a laboratory dish directly into functional nerve cells with the application of just three genes. The cells make the change without first becoming a pluripotent type of stem cell — a step long thought to be required for cells to acquire new identities.

The finding could revolutionize the future of human stem cell therapy and recast our understanding of how cells choose and maintain their specialties in the body.

“We actively and directly induced one cell type to become a completely different cell type,” said Marius Wernig, MD, assistant professor of pathology and a member of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine. “These are fully functional neurons. They can do all the principal things that neurons in the brain do.” That includes making connections with and signaling to other nerve cells — critical functions if the cells are eventually to be used as therapy for Parkinson’s disease or other disorders.

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