Neurons from stem cells for the treatment of Alzheimer's disease
Neurons that die in Alzheimer's disease were obtained from stem cells
LifeSciencesToday based on materials from Northwestern University:
From Stem Cells to Neurons Lost in Alzheimer'sScientists at Northwestern University (USA) for the first time transformed human embryonic stem cells into an important type of neurons, the early death of which in Alzheimer's disease is the main cause of memory loss.
These vital neurons, called basal cholinergic neurons of the forebrain, help the hippocampus extract memories from the brain. The population of such neurons in the brain is relatively small, and their loss has a rapid and devastating effect on the ability to remember.
The new possibility of reprogramming stem cells and growing an unlimited number of human neurons will give scientists the opportunity to quickly test drugs for the treatment of this neurodegenerative disease, will allow them to study why neurons die, and will contribute to the development of methods for transplanting new neurons to patients with Alzheimer's disease.
"Now that we know how to get these cells, we can study them in tissue culture and find out what can be done to prevent their death," says senior author of the study, Jack Kessler, MD, professor of Neurology and Stem Cell Biology at the Feinberg School of Medicine Medicine) Northwestern University.
The lead author of the article is Christopher Bissonnette, a former doctoral neurologist who worked for six years in Professor Kessler's laboratory, trying to "crack" the genetic code of stem cells and get neurons.
"This method of producing neurons allows you to grow an almost infinite number of such cells in the laboratory, which will give other scientists the opportunity to study why this particular cell population selectively dies in Alzheimer's disease," Bissonnette comments on his research.
The possibility of obtaining such cells means that researchers will be able to quickly test thousands of different drugs to determine which ones can preserve cells when they are in a problematic environment. Such a fast testing method is called high-performance screening.
Kessler and Bissonnette demonstrated that the newly obtained neurons function in the same way as their prototypes. They transplanted them into the hippocampus of mice and showed that the neurons function normally. The cells formed axons, or binding fibers, projected into the structures of the hippocampus, and produced acetylcholine, a chemical needed by the hippocampus to extract memories from other parts of the brain.
In a new, yet-to-be-published study, scientists have developed another method for producing neurons. They transformed human skin cells into embryonic stem cells (so-called induced pluripotent stem cells, iPS cells), and then reprogrammed them into neurons.
These stem cells and neurons were obtained from skin cells of three groups of people: patients with Alzheimer's disease, healthy people without a family history of Alzheimer's and healthy people with an increased likelihood of developing this neurodegenerative disease due to a family history of Alzheimer's disease caused by genetic mutations or unknown causes.
"This gives us a new method of studying diseased cells obtained directly from patients with Alzheimer's disease," says Professor Kessler. "That's why it's especially interesting."
Bissonnette's tenacity in the face of often disappointing results was fueled by his childhood memories of his grandfather dying of Alzheimer's disease.
"I saw how the disease was slowly and mercilessly destroying his memory and personality, and I was powerless to help him," recalls Bissonnette. "It made me become a scientist. I wanted to discover new treatments to reverse the damage caused by Alzheimer's disease. My goal was to make human stem cells become new healthy cells, suitable for replacement, so that one day they could be transplanted into the patient's brain and help his memory recover."
To transform a stem cell into a cholinergic neuron, Bissonnette had to grow and test millions of cells, looking for ways to turn on a specific gene sequence.
"A stem cell has the potential to become almost any cell in the body, from a heart cell to a layer of skin," he explains. "Its development is due to a cascade of events that slowly push it towards the final cellular type."
But it wasn't enough to get neurons. Bissonnette still had to learn how to stabilize them so that they lived for at least 20 days, and thereby prove that they were normal cells.
"Since this was a completely new study, no one knew what type of tissue culture mature human neurons would like to live in," he says. "As soon as we realized this, they began to live indefinitely."
The study was funded by the National Institutes of Health (National Institutes of Health) USA. An article about the study (The Controlled Generation of Functional Basal Forebrain Cholinergic Neurons from Human Embryonic Stem Cells) is published in the journal Stem Cells.
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