Human stem cells returned monkeys the ability to grab objects

<pre>Human stem cells returned monkeys the ability to grab objects

Stem cell therapy is very attractive in its intuitive simplicity: you cleanse the damaged cells, run a gang of healthy ones instead, sit idly by and wait until the body heals itself. In the case of spinal cord injuries, the potential of stem cells to restore the possibility of movement promises fantastic prospects. However, the human body is not a machine and is not a simple system that allows replacing parts on the move. After transplantation, stem cells are often rejected, die in a hostile environment of the host's body before they have a chance of recovery.

Over the past thirty years, neuroscientists have tried many methods, tried a cocktail for a cocktail of special molecules that can accelerate the survival of stem cells. And although there was a lot of success on rodent models, it was not possible to scale this therapy so that it worked with primates – and this is important for human trials.

Or it did not work out. Last month, the journal Nature Medicine published an “important” study detailing the recipe for transplanting human stem cells that survived and integrated into the damaged vertebral column of the monkeys.

Nine months after the operation, the cells dissolved hundreds of thousands of branches that formed synapses with the surviving neurons of the spinal cord of monkeys. Moreover, the spinal cerebral neurons of carriers recognized the human cells as their own, formed new compounds that restored the ability of the animal to snap objects.

“The growth that we observed in these cells is impressive, and ten years ago I would have thought that it's impossible, “says lead author Dr. Mark Tushinsky from the Institute for Transplant Neuroscience at the University of California, San Diego. “We definitely added confidence that this treatment will work for people.”

Early work

Spinal cord injury cuts long, thin neural branches – axons – that the brain uses to communicate with the rest of the body. To restore motor function, scientists need to convince the body to restore or grow these joints.

But that's the problem. After damage, the spinal cord quickly reorganizes the extracellular matrix – a complex network of structural molecules – around the site of injury. Like the “bricks” on the road, these proteins effectively block the transplanted stem cells from stretching their long axon branches. Moreover, the injury site is also devoid of supporting growth factors and other useful molecules that act as a nutrient cocoon for stem cells.

In order to circumvent this double defense, scientists have formed dozens of growth-provoking cocktails that could give a boost to transplanted cells. And this strategy seems to have worked.

Back in 2014, Tushinsky transformed the skin cells of a healthy human donor, transformed them into iPSC cells (induced pluripotent stem cells), and introduced these artificial stem cells into a matrix containing growth factors.

After putting the graft into two rats with two-week spinal injuries, human cells matured into new neurons and extended axons in the spinal cord of rats. But strangely enough, the scientists did not see any improvement in function, in part because of scarring at the site of transplantation.

“We are trying to do our best to determine the best way to transfer therapies involving neuronal stem cells in patients with spinal cord injury,” Tushinsky said at the time.

A New Hope

True to his word, Tushinsky tested his transfer protocol on monkeys, which are better suited as models for the human spinal cord.

The team crashed into the section of the monkey's spinal cord and in two weeks – enough time for patients to stabilize – injected stem cells human in damaged places along with growth factors.

It did not work. In the first four monkeys, the injections were not even fixed in place.

“If we tried to transplant on humans without a prior animal test, there would be a significant risk of failure of the clinical trial,” says Tushinsky.

Scientists quickly realized that they you need to increase the amount of an important protein ingredient in your prescription to better “glue” the graft in place. The team also found problems with immunosuppression, timing and surgical procedure. For example, they had to tilt the surgical table during surgery so that the cerebrospinal fluid did not flush the transplant. In addition, monkeys required a high dose of immunosuppressive drugs to prevent the body from attacking human cells.

Some grafts, each containing about 20 million human stem cells, were held in place by the remaining five monkeys.

Results were incredible. Already two months after the transplant, scientists discovered an explosion of new neural branches. Stem cells at the injury site developed to mature neurons, diluted to 150,000 axons that extended through the spinal cord of the monkey.

Some of the branches passed 50 mm from the graft site, approximately at the length of two spinal cord fragments in humans. Along the way, they established extensive connections with undamaged monkey cells.

What is even more steep, the monkey's own axons also formed synapses with the human neuron graft, forming mutual connections. These connections are extremely important for free hand movements in humans and this is one of the first vivid indications that transplanted stem cells can form such patterns. [9] After nine months, new neural connections helped the monkeys with injuries to return movements to their limbs, so that those could grasp soft objects (for example, oranges). Conversely, monkeys with poor grafts had poor control over the precise movements in the palms and fingers – they could only push the orange.

The results may seem not very impressive, but the authors say that nine months is an instant for functional recovery.

“Grafts and the new schemes that they were part of were still ripening toward the end of our observations, so the recovery may continue, “says study author Dr. Efron Rosenzweig.

Although the functional improvements were only partial, Dr. Gregoire Qu from the Swiss Federal Institute of Technology (EPFL) in Geneva calls the study “a landmark in regenerative medicine.”

“And this is not surprising, given that the functional integration of new cells and compounds in the work of the nervous system will require time and specific rehabilitation procedures” , he says, adding that the study offers valuable information for potential human exploration.

Steve Goldman of the University of Rochester agrees with him:

“This is a big jump from rodents to mat. This is a heroic study, for that matter. “

For Tushinsky the same work is just beginning. Firstly, not all stem cells are created the same, and his team tries to determine which of them are most effective in restoring the function.

On the other hand, he also studies additional ways to further enhance the functionality of the regenerated neurons, so that their axons can spread through the damaged area and completely replace those that were lost during the trauma.

“It's too early to go over to people,” he cautions, because additional tests are needed. And this patience will pay off in full.

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