Stem cell stories that caught our eye: Trifecta of nerve news on aging, Parkinson’s and myelin diseases, also expanding cord blood

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

rapamycin-effect-on-MILS-neurons

Untreated (top) and treated nerves

To save nerves, make them slow down. Nerves, like all cells, constantly make protein, but that task uses up a lot of energy and older nerves have a limited energy supply. A CIRM-funded team at the Salk Institute has shown that an approved drug can slow down protein production in nerves, conserve energy and help them survive.

The Salk team led by Tony Hunter saw the tamping down effect in a disease-in-a-dish model of Leigh syndrome, an inherited neurodegenerative condition caused by a mutation in mitochondria, the cell’s power plant. They created iPS type stem cells by reprogramming skin cells from a Leigh syndrome patient, grew them into nerves and saw evidence of energy depletion that was reversed when they treated the cells with the drug rapamycin.

 “Reducing protein production in ageing neurons allows more energy for the cell to put toward folding proteins correctly and handling stress,” said team member Xinde Zheng, in a Salk release posted by Scicasts. “The impact of our finding is that modulation of protein synthesis could be a general approach to treating neurodegeneration.”

Next step for the team will be seeing if their finding holds true in an animal model of the syndrome. They published their findings in eLife.

 

For dopamine nerves turn them on and off.  Many researchers strive to turn stem cells into dopamine producing nerves to replace the chemical signal that is in short supply in Parkinson’s disease patients. But what if they succeed, put the new nerves in patients and they produce too much dopamine? A team, at the University of Wisconsin has a solution, make the new nerves responsive to a drug that can act as an on-and-off switch.

The team grew nerves from stem cells made from iPS type stem cells and genetically engineered them so that they would only produce dopamine in the presence of a certain drug. Brad Fikes at the San Diego Union Tribune wrote a brief story about the research that the team published in Cell Stem Cell.

 He put the news into perspective by noting that early trials implanting dopamine nerves from fetal tissue resulted in some patients having side effects from over production of the nerve signal transmitter.

 

And restoring nerves protective myelin.  Neurons form the basis of all brain function, but they take a family of support cells and tissues to do a good job of directing our muscles, recording memory, etc.  First nerves need the protective insulation called myelin to properly transmit signals. Cells called oligodendrocytes produce the myelin, but they need signals from cells called astrocytes to do their job well. Researchers have known for some time that immature astrocytes do a great job of fostering oligodendrocytes, but mature astrocytes do not, but they have not known why.

Now, CIRM-funded researchers at the University of California, Davis, have isolated a protein secreted by immature astrocytes called TIMP-1 that promotes proliferation of the needed oligodendrocytes, and down the line, the myelin needed to protect neurons.

In the study published in Cell Reports, the researchers created iPS type stem cells and directed them to become astrocytes, stopping the growth at an immature state and implanted them in mice. But before the transplants, they shut down the production of TIMP-1 in some of the astrocytes, and in those mice they saw no increase in the production of myelin.

 

Deng-headshot

Wenbin Deng of UC Davis

The research project leader, Wenbin Deng, speculated in a Davis press release on how the research could eventually help patients with any number of diseases involving myelin loss:

 “We are hopeful that his could lead to a promising therapy for premature brain injury, cerebral palsy, multiple sclerosis, spinal cord injury, white matter stroke and many neurodegenerative diseases.”

 

Key protein for developing blood stem cells.  The stem cells found in umbilical cord have saved thousands of cancer patients by rebuilding their immune system after chemotherapy. But cord blood samples often have too few stem cells to be effective and while a couple teams have reported some progress in expanding the number of stem cells in any one cord sample, more progress is needed.

Researchers at McMaster University reported in the journal Nature this week that they had isolated a protein that controls the development of blood stem cells. That protein, Musashi-2, does not regulate genetic activity at the DNA level, but rather at the next step in the gene-to-protein pathway, regulating the activity of RNA.

In an article posted on the Bioscience Technology website, the team leader Kristin Hope speculated on the value to patients when they learn how to turn this knowledge into making cells for therapy:

“Providing enhanced numbers of stem cells for transplantation could alleviate some of the current post-transplantation complications and allow for faster recoveries, in turn reducing overall health care costs and wait times for newly diagnosed patients seeking treatment.”

 

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