Stem cell stories that caught our eye: Blood stem cells on a diet, Bladder control after spinal cord injuries, new ALS insights

Putting blood stem cells on a diet. (Karen Ring)

valine

Valine. Image: BMRB

Scientists from Stanford and the University of Tokyo have figured out a new way to potentially make bone marrow transplants more safe. Published yesterday in the journal Science, the teams discovered that removing an essential amino acid, called valine, from the diets of mice depleted their blood stem cells and made it easier for them to receive bone marrow transplants from other mice without the need for radiation or chemotherapy. Removing valine from human blood stem cells yielded similar results suggesting that this therapeutic approach could potentially change and improve the way that certain cancer patients are treated.

In an interview with Science Magazine, senior author Satoshi Yamazaki explained how current bone marrow transplants are toxic to patients and that an alternative, safer form of treatment is needed.

“Bone marrow transplantation is a toxic therapy. We have to do it to treat diseases that would otherwise be fatal, but the quality of life afterward is often not good. Relative to chemotherapy or radiation, the toxicity of a diet deficient in valine seems to be much, much lower. Mice that have been irradiated look terrible. They can’t have babies and live for less than a year. But mice given a diet deficient in valine can have babies and will live a normal life span after transplantation.”

The scientists found that the effects of a valine-deficient diet were mostly specific to blood stem cells in the mice, but also did affect hair stem cells and some T cells. The effects on these other populations of cells were not as dramatic however as the effects on blood stem cells.

Going forward, the teams are interested to find out whether valine deficiency will be a useful treatment for leukemia stem cells, which are stem cells that give rise to a type of blood cancer. As mentioned before, this alternative form of treatment would be very valuable for certain cancer patients in comparison to the current regimen of radiation treatment before bone marrow transplantation.

Easing pain and improving bladder control in spinal cord injury (Kevin McCormack)
When most people think of spinal cord injuries (SCI) they focus on the inability to walk. But for people with those injuries there are many other complications such as intense nerve or neuropathic pain, and inability to control their bladder. A CIRM-funded study from researchers at UCSF may help point at a new way of addressing those problems.

The study, published in the journal Cell Stem Cell, zeroed in on the loss in people with SCI of a particular amino acid called GABA, which acts as a neurotransmitter in the central nervous system and inhibits nerve transmission in the brain, calming nervous activity.

Here’s where we move into alphabet soup, but stick with me. Previous studies showed that using cells called inhibitory interneuron precursors from the medial ganglionic eminence (MGE) helped boost GABA signaling in the brain and spinal cord. So the researchers turned some human embryonic stem cells (hESCs) into MGEs and transplanted those into the spinal cords of mice with SCI.

Six months after transplantation those cells had integrated into the mice’s spinal cord, and the mice not only showed improved bladder function but they also seemed to have less pain.

Now, it’s a long way from mice to men, and there’s a lot of work that has to be done to ensure that this is safe to try in people, but the researchers conclude: “Our findings, therefore, may have implications for the treatment of chronically spinal cord-injured patients.”

CIRM-funded study reveals potential new ALS drug target (Todd Dubnicoff)
Of the many diseases CIRM-funded researchers are tackling, Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s Disease, has got to be one of the worst.

yeo_healthy_ipsc_derived_mo

Motor neurons derived from skin cells of a healthy donor
Image: UC San Diego

This neurodegenerative disorder attacks and kills motor neurons, the nerve cells that control voluntary muscle movement. People diagnosed with ALS, gradually lose the ability to move their limbs, to swallow and even to breathe. The disease is always fatal and people usually die within 3 to 5 years after initial diagnosis. There’s no cure for ALS mainly because scientists are still struggling to fully understand what causes it.

Stem cell-derived “disease in a dish” experiments have recently provided many insights into the underlying biology of ALS. In these studies, skin cells from ALS patients are reprogrammed into an embryonic stem cell-like state called induced pluripotent stem cells (iPSCS). These iPS cells are grown in petri dishes and then specialized into motor neurons, allowing researchers to carefully look for any defects in the cells.

This week, a UC San Diego research team using this disease in a dish strategy reported they had uncovered a cellular process that goes haywire in ALS cells. The researchers generated motor neurons from iPS cells that had been derived from the skin samples of ALS patients with hereditary forms of the disease as well as samples from healthy donors. The team then compared the activity of thousands of genes between the ALS and healthy motor neurons. They found that a particular hereditary mutation doesn’t just impair a protein called hnRNP A2/B1, it actually gives the protein new toxic activities that kill off the motor neurons.

Fernando Martinez, the first author on this study in Neuron, told the UC San Diego Health newsroom that these news results reveal an important context for their on-going development of therapeutics that target proteins like hnRNP:

“These … therapies [targeting hnRNP] can eliminate toxic proteins and treat disease. But this strategy is only viable if the proteins have gained new toxic functions through mutation, as we found here for hnRNP A2/B1 in these ALS cases.”

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