Mice with multiple sclerosis were helped by cell therapy
Human neural Progenitor Cells
mice were cured of multiple sclerosis
LifeSciencesToday based on TSRI Materials: Stem Cell Therapy Shows Promise for MS in Mouse ModelScientists at The Scripps Research Institute (TSRI), The University of Utah and the University of California, Irvine have transplanted human stem cells into the spinal cord of mice with a disease close to human multiple sclerosis.
As a result, the animals were able to walk and even run again. It is important to note that the mice recovered after their body rejected human stem cells.
"When we transplanted human cells into paralyzed mice, they got up and started walking after a couple of weeks and completely recovered within a few months," says his co–director, Professor of neuroscience at TSRI Jeanne Loring, PhD, about the results of the study.
Another co-leader of the work, professor of pathology at the University of Utah, immunologist Thomas Lane, PhD, claims that he has never seen anything like it.
"We have been studying mouse stem cells for a long time, but we have never seen the clinical improvement that occurred when using human cells provided to us by Dr. Loring's laboratory," comments Dr. Lane.
The almost complete recovery of mice, reported in an early online edition of the journal Stem Cell Reports (Lu Chen et al., Human Neural Precursor Cells Promote Neurological Recovery in a Viral Model of Multiple Sclerosis), can become the basis for the development of new treatments for multiple sclerosis in humans.
"This is a big step forward in the development of new treatments to stop the progression of this disease and stimulate the recovery of patients with multiple sclerosis," said study co–author Craig Walsh, an immunologist at UC Irvine.
Multiple sclerosis is an autoimmune disease of the brain and spinal cord that affects more than half a million people in North America and Europe and more than two million worldwide. In multiple sclerosis, immune cells known as T cells invade the spinal cord and brain, causing inflammation and, ultimately, the loss of the insulating sheath of nerve fibers formed by myelin. Affected nerve fibers lose their ability to effectively transmit electrical signals, and eventually this can lead to symptoms such as limb weakness, numbness and tingling, fatigue, slurred speech, vision and memory problems, depression.
1) Multiple sclerosis disrupts the function of nerves, damaging the myelin – the insulating layer surrounding them.
Mice with this disease have impaired motor skills.
2) Human neural stem cells injected into mice with multiple sclerosis,
stimulate the animals' own cells and eliminate nerve damage.
3) The functions of nerve cells have been restored. Mice can walk and run.
(Photo: University of Utah Health Sciences Office of Public Affairs)Modern pharmacological agents, such as interferon beta, are aimed at suppressing an immune attack that deprives nerve fibers of myelin.
But their effectiveness is limited, and negative side effects are often significant. Professor Loring's group was looking for another way to treat multiple sclerosis – using human pluripotent stem cells with the potential to differentiate into any of the body's cell types.
Loring's group focused on differentiating human stem cells into neural progenitor cells-an intermediate type of cell that can eventually develop into neurons and other types of cells of the nervous system. In collaboration with Professor Lane's group, Professor Loring and her colleagues tested the effects of transplanting human neural progenitor cells into the spinal cord of mice infected with the virus that causes the symptoms of multiple sclerosis.
The changes observed in the state of almost completely paralyzed mice after the introduction of human neural progenitor cells into their affected spinal cord were simply striking.
"Tom called me and said: "You won't believe it," says Professor Loring. "He sent me a video of mice running around in cages. "Are you sure these are the same mice?" I asked."
Even more surprising was that the animals retained the ability to move even after the human cells were rejected by their body, which happened about a week after transplantation. This suggests that human stem cells secreted a protein or proteins that have the ability to prevent or hinder the progression of multiple sclerosis in mice for a long time, says Ron Coleman, PhD, PhD student of Professor Loring, the first author of the article.
"After the first domino bones are exposed by human stem cells, the cells can be removed, and the process will continue, because they initiated a cascade of events," Dr. Coleman draws an analogy.
In a new study, scientists have shown that transplanted human stem cells triggered the formation of white blood cells, known as regulatory T cells, responsible for suppressing the autoimmune response at the end of inflammation. In addition, the transplanted cells released proteins that signal to the mice's own cells about the need to remyelinate nerve fibers deprived of their protective membranes.
Obtaining a line of human neural progenitor cells used to treat mice can be considered a happy case. When obtaining neural progenitor cells from human stem cells, Dr. Coleman used a traditional technique, but decided to deviate somewhat from the standard protocol. In particular, he transferred the developing cells to another Petri dish.
The top row shows stem cells transplanted into the spinal cord of a mouse. In the bottom row – a close-up of stem cells (brown). 7 days after transplantation, stem cells are not detected. During this short period of time, the stem cells sent chemical signals to the mouse's own cells, which allowed them to eliminate nerve damage caused by multiple sclerosis. (Photo: Lu Chen)"I wanted all the cells to have similar properties, and if I didn't tolerate them, they looked very different," says Dr. Coleman, for whom the death of his mother from this disease was an incentive to study multiple sclerosis.
This step, called passage, turned out to be the key. "It turns out that the passage changes the types of proteins expressed by cells."
Professor Loring called obtaining a successful neural progenitor cell line a "happy accident." "If we used traditional methods of obtaining cells, they would not work," she explains. "Now we have shown it. There are a dozen different ways to get neural progenitor cells, but today only this one works. Now we know that it is incredibly important to always get cells in the same way."
Now scientists are working on the identification of specific proteins secreted by their unique line of human progenitor cells. One of the promising candidates is a family of proteins known as transforming growth factors beta, or TGF-beta, which, as other studies have shown, are involved in the formation of regulatory T cells. Experiments have demonstrated that human neural progenitor cells secrete TGF-beta1 and TGF-beta2 proteins while located in the spinal cord of diseased mice. However, it is likely that other, as yet unknown, protein factors may be involved in the healing of mice.
If researchers are able to determine which proteins secreted by neural progenitor cells are responsible for the recovery of animals, it will be possible to develop methods for treating multiple sclerosis that are not associated with the use of human stem cells.
"Once we identify the factors responsible for healing, we can make a drug out of them," explains Professor Lane. Another possibility, according to Professor Loring, may be to inject these healing-promoting protein factors into the spinal cord of patients with multiple sclerosis.
A deeper understanding of what determines the effectiveness of human neural progenitor cells in curing mice will be the key to developing any of these human therapies.
"Now we are on the trail of what these cells do and how they work," concludes Professor Loring.
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