Stem Cells and Stroke: An Interview with Neuroscientist Dr. Dileep Yavagal
The Miller School stroke expert uses stem cells to help patients retain brain function after stroke.
Early in his medical career, Dileep Yavagal, M.D., chief of interventional neurology and professor of clinical neurology and neurosurgery at the University of Miami Miller School of Medicine, almost decided to study cardiology. He chose neuroscience instead, because of its complexity and how much about the brain’s basic function was yet to be understood.
He and his team have spent years researching and developing a strategy to infuse stem cells directly into arteries supplying the brains of patients who have strokes to rescue brain tissue and function. Now, those techniques are moving into clinical trials trials and Dr. Yavagal received a “Best Abstract” award from the Society of Vascular and Interventional Radiology for his first-in-man study of intra-arterial allogeneic mesenchymal stem cell therapy for two patients who suffered from locked-in syndrome after thrombectomy.
Dr. Yavagal talked about his journey in neuroscience and stroke research in the following interview, which has been edited for length and clarity.
How did you become interested in neuroscience and medicine?
I was interested at a very young age in nerve transmission which, at a very basic level, is how signals get transmitted over nerves. Then, when I got interested in medicine and I started to think about what specialty I might choose, I moved towards the brain.
Neuroscience research was a logical path, because there’s just so many brain conditions that are unsolved, and not really treatable. We need to identify treatment targets and agents that could help. So that’s what I focused on during my academic pursuits, during my residency. And then when I did my fellowship in neurointervention, I got an internal grant at UCLA to develop a large animal stroke model, which was really not there, and this would be with a catheter approach. When I got recruited to the University of Miami as faculty, the Stem Cell Institute had just started, and it made a lot of sense to pursue stem cells as an agent to reverse stroke in the brain using this model.
What has surprised you throughout your research career thus far?
When we give stem cells intra-arterially, we bring the catheter up into the carotid artery under specialized, X-ray guidance. We move cells into the carotid artery close to the brain, and the reduction in the injury from stroke in the animal models is incredibly dramatic.
We see it at different levels. We see it on the MRI. We see it when we do the histology of the brain. A lot of brain tissue that would have otherwise died is now salvaged. And in animal models, we also see that the animal is doing much better with the functions correlating with the brain areas saved. And so these cells, when given directly into the carotid artery, have a pretty dramatic effect, reducing damage by almost 50% as compared to placebo or controls. When we look at the neuronal level and count the actual neurons, the neurons are significantly higher in the stroke area compared to the animals that just got saline, as opposed to stem cells.
We are one of two or three groups that have moved the stem cell field forward. That’s been very, very fulfilling, and a source of pride for the lab. And we are certainly not done.
Dr. Dileep Yavagal
It’s very fulfilling to see that kind of brain repair. And this is about 30 days after giving the cells, so it’s a very tangible timeline to repair stroke. My focus has been on giving the treatment at the early phase, within the first two days of a stroke, when the cells act more as anti-inflammatory and salvaging agents for severely injured brain tissue. They don’t necessarily form new brain tissue, but they secrete a lot of molecules that help salvage the injured tissue.
Is this work translating into a clinical trial?
I did a clinical trial a few years ago that showed safety, but we are applying for a larger clinical trial because the approach is slightly different now as compared to that trial. The first in-man trial done under compassionate use approval has been terrifically exciting. We got permission from the FDA to treat two patients who had a very severe kind of stroke that occurred in the back of the brain, causing what is called locked-in syndrome. You’re fully conscious, but you can’t move anything except for your eyes and eyelids.
That stroke is in the brainstem. We gave stem cells in the basilar artery, which is what supplies the brainstem. While the improvement of the stroke on MRI happened within 10 days, the clinical improvement in the first patient took time. But within six months, they were off the ventilator, and now at two years, they’re sitting up and eating with their right hand. In the second patient, while the treatment was safe, the family decided to withdraw care early on at 10 days.
What’s the next step from here?
We are going to propose a 20-patient study of locked-in syndrome because it’s so devastating and often happens in young people. Then, secondly, we are also proposing a bigger trial for the regular kind of strokes in the front of the brain.
What are you most proud of in your work?
I started a stroke campaign called Mission Thrombectomy, which has grown to 91 countries. That’s been for the thrombectomy surgery, which does not involve stem cells currently. It is a emergency brain catheter surgery to unblock the blocked brain artery. The campaign’s success has been pretty amazing in terms of advocacy and getting more population-level education and access around the world. That’s something that I’m very proud of.
However, all the milestones that we have hit in stem cell work have been a great source of satisfaction. We are one of two or three groups that have moved this field forward. And so that’s been very, very fulfilling, and a source of pride for the lab. And we are certainly not done. We have to take this to patients, get an FDA approval.
But there was so much anxiety among people working in this field that, when you give cells in a human being, the cells themselves could block arteries and worsen the stroke. We did research systematically over a decade and a half where we figured out the safe dose. When we gave it, it was not only safe, but also in one patient had a dramatic improvement. So I am very proud of that journey.
What would it take for this to become a standard of care? Could the average hospital apply this quickly? Do they need a ton of specialized equipment or specialized people?
That’s the best part. The equipment and the people are there. The technique is not hard at all, so the 20-patient study would need to get replicated in a slightly bigger study. But I’m hoping that we get funded for the 300-patient trial for the more common kind of stroke, and that would then accelerate the path towards this becoming a standard of care. There would probably need to be one more study after that. I’m hoping before the end of the decade this could become standard of care.
Right now, with thrombectomy, about 50% of patients, if they receive the treatment within 24 hours, recover to the point of being able to live independently. But our calculation, based on our laboratory work, is that giving stem cells would bring it up to even up to 70% or 80%. And they would be able to get the treatment up to 48 hours after the stroke, instead of 24. This would be a big deal, because globally, only 2.79% of patients get the thrombectomy within 24 hours. Just doubling the time window to 48 hours, we think, would increase that accessibility to at least 10% to20% of patients.
Tags: Dr. Dileep Yavagal, mechanical thrombectomy, neurology, neurosurgery, stroke, stroke outcomes, thrombectomy