“Latest Stem Cells News”

A team of Harvard stem cell researchers has succeeded in reprogramming adult mouse skin cells directly into the type of motor neurons damaged in amyotrophic lateral sclerosis (ALS), best known as Lou Gehrig’s disease, and spinal muscular atrophy (SMA). These new cells, which researchers are calling induced motor neurons (iMNs), can be used to study the development of the paralyzing diseases and to develop treatments for them.

Producing motor neurons this way is much less labor intensive than having to go through the process of creating induced pluripotent stem cells (iPSC, iPS cells), and is so much faster than the iPS method that it potentially could reduce by a year the time it eventually takes to produce treatments for ALS and SMA, said Kevin Eggan, leader of the Harvard team.

Importantly, the direct reprograming does not involve the use of any factors known to trigger cancer or any other disease states, and the factors in fact make the fibroblasts, the connective tissue cells that make and secrete collagen proteins, stop dividing.

The work by Eggan, a member of the Harvard Stem Cell Institute principal faculty and an associate professor in Harvard’s Department of Stem Cell and Regenerative Biology (SCRB), and his colleagues builds on and advances work by SCRB co-chair and Professor Doug Melton, who pioneered direct cellular reprogramming, and Marius Wernig of Stanford, who used direct reprogramming to produce generalized neurons.

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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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Using two distinct methods, Whitehead Institute researchers have successfully and consistently manipulated targeted genes in both human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells (adult cells that have been reprogrammed to an embryonic stem cell-like state).

In one case, scientists employed proteins known as zinc finger nucleases (ZFNs) to change a single base pair in the genome, allowing them either to insert or remove mutations known to cause early-onset Parkinson’s disease (PD). The second method relies on proteins called transcription activator like effector nucleases (TALENs) capable of altering specific genes with similar efficiency and precision as ZFNs. Both sets of experiments were conducted in close collaboration with scientists at Sangamo BioSciences.

Targeted genetic manipulation addresses a problem that has been plaguing human stem cell research – the ability to cleanly and site-specifically modify the genomes of human ES and iPS cells. Realizing the therapeutic promise of these cells depends on such changes to fix disease-causing mutations before the cells could be transplanted into patients or to create cell lines that researchers can use to study genetic diseases.

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University of Minnesota Medical School researchers have developed a new strategy to improve the development of induced pluripotent stem cells (iPS).

Currently, iPS cells are created by introducing four defined genes to an adult cell. The genes reprogram the adult cell into a stem cell, which can differentiate into many different types of the cells in the body. Typically, the four genes introduced are Oct4, Sox2, Klf4 and c-Myc, a combination known as OSKM.

The U of M researchers found that by fusing two proteins – a master stem cell regulator (Oct4) and a fragment of a muscle cell inducer (MyoD) – they succeeded in “powering up” the stem cell regulator, which can dramatically improve the efficiency and purity of reprogrammed iPS cells.

“Our team discovered that by fusing a fragment of the powerful protein MyoD to Oct4 we could create a ‘super gene’ which would improve the iPS reprogramming process,” said senior author Dr. Nobuaki Kikyo, Stem Cell Institute researcher and University of Minnesota Medical School associate professor. “The result is what we termed M3O, or ‘super Oct4’ – a gene that improves the creation of iPS cells in a number of ways. In the process we shed new light on the mechanism of making iPS cells.”

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Thursday August 4, 2011
3:01

Jocelyn Kaiser:
Hi everyone. This is Jocelyn Kaiser, a news writer for Science magazine. In today’s chat, we’re talking about last week’s court decision finding that federal funding for human embryonic stem cell research is legal. We’ll discuss what’s next for Sherley v. Sebelius and what it’s like to work in an area of research where policies are always changing. Guest Hank Greely, a law professor at Stanford, is here now and we’re hoping to be joined later by Amander Clark, a stem cell researcher at UCLA. Let’s start with a question for Hank.

Hank, why was this lawsuit so important?
3:02

Hank Greely:
Well, when Judge Lamberth ruled last August that the NIH policy was illegal, he stopped, for several weeks, all federal funding for human embryonic stem cell research. That was a pretty dramatic effect, and, as long as this suit is pending, it makes that funding somewhat uncertain.
3:03

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