Stem Cell Therapy Shows Promise for Stroke Recovery

 The promise has been out there for well over a decade, WHOM will actually solve the problem? NO leadership and NO strategy is the result of our fucking failures of stroke associations!

• stem cells (409 posts to April 2011)

Stem Cell Therapy Shows Promise for Stroke Recovery

University of Miami Miller School of Medicine

Researchers from the University of Miami Miller School of Medicine and collaborating institutions have published a comprehensive review examining the rapidly evolving field of intra-arterial stem cell therapy for ischemic stroke, highlighting its potential to improve recovery for patients who continue to face disability despite major advances in stroke treatment.

Published in the American Heart Association Journal Stroke: Vascular and Interventional Neurology, the review, titled "Progress in Intra-arterial Stem Cell Therapy for Ischemic Stroke – A Review," examines decades of preclinical and clinical research and outlines a roadmap for translating regenerative therapies from the laboratory to the bedside.

Ischemic Stroke, in which blood supply to a part of the brain is cut off by suddenly by a clot blockage, remains one of the leading causes of death and long-term disability worldwide. While clot-busting medications and mechanical thrombectomy have transformed care for acute ischemic stroke, many patients are left with significant neurological deficits despite successful restoration of blood flow. The authors argue that stem cell therapies delivered directly into the brain's circulation via minimally invasive and widely available catheter angiographic techniques may complement existing treatments. The stem cells targeted this way to the stroke injured brain area work by promoting brain repair, reducing inflammation, and enhancing recovery.

"Mechanical thrombectomy has revolutionized stroke treatment, but half of the treated or more patients still do not regain full independence," said Dileep R. Yavagal, M.D., professor of clinical neurology and neurosurgery at the University of Miami Miller School of Medicine and senior author of the review. "Stem cell therapy represents a promising strategy to help the brain recover after injury and may become an important next step in improving outcomes(NOT GOOD ENOUGH!) for stroke patients."

(Likely a much better approach to full recovery is stopping the 5 causes of the neuronal cascade of death in the first week and thus saving hundreds of millions to billions of neurons! So you aren't even thinking of this properly!)

A Targeted Approach

Stem cells can be delivered through several different routes and optimal route in Stroke treatment is not yet established. The review focuses on intra-arterial delivery, an approach in which stem cells are infused directly into arteries supplying the injured region of the brain. Unlike intravenous administration, in which much of the cells are trapped in organs such as the lungs and liver, intra-arterial delivery into the affected artery allow a greater concentration of therapeutic cells to reach stroke-affected tissue. Surgical approaches such through a small hole in the skull are more invasive.

Researchers note that intra-arterial delivery is particularly attractive because it can potentially be performed during the same minimally invasive endovascular procedures and techniques used now as standard of care treatment, mechanical thrombectomy, avoiding the need for a new surgical access or additional intervention.

Preclinical studies, including from Dr. Yavagal's laboratory at the University of Miami Miller School of Medicine Interdisciplinary Stem Cell Institute, reviewed by the authors demonstrate that stem cells may reduce inflammation, promote formation of new blood vessels, support neural repair, and improve neurological outcomes following stroke. Multiple early-stage clinical trials have also established the feasibility and safety of stem cell administration across several delivery routes.

Strong safety record, more research needed

The review analyzes more than two decades of clinical development and notes that more than 40 randomized clinical trials have investigated stem cell therapies for stroke via many different routes of delivery. While safety has been consistently demonstrated, evidence for definitive functional benefit remains under investigation. Several ongoing studies are working to determine optimal cell type, dosing, timing, and patient selection strategies.

"The safety of IA stem cell therapy has been established by several preclinical and clinical studies and will continue to remain a critical endpoint for all future studies," said Roshni Thakkar, Ph.D., co-first author and research assistant professor in the Department of Neurology at the University of Miami. "The next challenge that the field is taking on is to identify the right cells, the right dose, the right patients, and the right time to intervene in order to maximize stroke recovery."

The authors emphasize that future studies should integrate advanced imaging, biological markers, and immune profiling to better understand how stem cells interact with the post-stroke brain and to identify patients most likely to benefit.

"Regenerative medicine has the potential to fundamentally reshape stroke treatment," said Nadia McMillan, M.D., Ph.D., co-first author, senior neuro-endovascular fellow and instructor . "The goal is not only to save brain tissue during a stroke but to help patients regain function and quality of life afterward."

Looking toward the future

According to the review, emerging therapies may eventually include bioengineered stem cells, extracellular vesicles and exosomes, and combination approaches that pair thrombectomy with regenerative treatments. Continued advances could ultimately transform stroke care from a model focused primarily on restoring blood flow to one that also actively promotes brain repair and recovery.

The authors conclude that while significant challenges remain, ongoing clinical trials and rapid advances in regenerative neuroscience provide reason for optimism that stem cell-based therapies may one day become an important adjunct to standard stroke treatment and achieve an outcome free of disability for the vast majority of stroke patients.

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Tags: regenerative medicine , america , investigation , american , Administration , Miami , biological , neuroscience , clinical trials , neurosurgery , University of Miami , blood vessels , inflammation , cell therapy , American Heart Association , quality of life

Study reveals why many patients fail to recover after stroke

Simple, because NO ONE looked at the recovery protocol that Pedro Bach-y-Rita  used to recover fully back in 1958 with only a partial brain! But you don't have anyone COMPETENT AT ALL, DO YOU?

Study reveals why many patients fail to recover after stroke

A clot forms. Blood flow to the brain is blocked. Starved of oxygen, neurons begin to die.

This scenario, known as an ischemic stroke, plays out in roughly 21,000 people worldwide each day, threatening them with long-term disability or even death. In recent decades, the advent of drugs and mechanical tools for removing clots has revolutionized stroke care.

Yet, even with the clot gone and the vessel clear, up to 50% of patients never recover neurologically. New research from the University of Colorado Boulder and the University of Antwerp helps explain why.

The study, published in the journal PNAS, reveals in unprecedented detail how the brain's own defense mechanisms against stroke can backfire, triggering yet more clots-micro-clots-in minor vessels, damaging tissue long after the primary culprit is gone.

We now have a way to explain why so many of these patients are not seeing neurological improvements. Our findings also point to a new potential target for therapeutics that could be extremely impactful for stroke patients."

Debanjan Mukherjee, co-author, assistant professor of mechanical engineering, CU Boulder

The mystery behind "no reflow"

Doctors have long known that removing a stroke-causing clot cannot always restore full blood flow to the brain. But why this phenomenon, known as "no reflow," occurs has remained a mystery. (Just maybe because Capillaries that don't open due to pericytes and then there is the neuronal cascade of death in the first week)

To unravel it, Mukherjee, who studies the physics of blood flow, teamed up with senior author Frederik Denorme, an assistant professor of biology at the University of Antwerp who studies, as he puts it, "life after the clot."

"The dogma used to be that you just need to get rid of that blood clot and then all problems should be solved," said Denorme. "We now know that is not the case."

In fact, only about 1 in 10 surviving stroke patients recover completely after a stroke; 25% have minor impairments; and half have moderate to severe impairments.

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To examine what, precisely, goes on in the brain after a clot is removed, the research team first turned to mice.

Using a technique called intravital microscopy, they observed in real time how blood flowed in the brain and cells behaved in the hour after the mice suffering from stroke underwent endovascular thrombectomy-a procedure in which a tool is threaded through a blood vessel to pluck out an obstructive clot.

While blood quickly started flowing again post-procedure, the researchers were stunned to see that in many mice, it flowed haphazardly, in fits and starts, even reversing course at certain points.

"We saw it happening with our own eyes. Blood that was flowing left all of a sudden flowed right and vice versa," said Denorme. "It was remarkable."

A Jekyll and Hyde protein

An even closer look revealed that, as the brain tried to divert blood around the original obstruction, tiny clots formed where the haphazard channels converged.

To drill down on why those clots formed, Mukherjee's FLOWLab recreated this scenario using computer simulations. In other research, his lab has recreated similar scenarios using a 3D artificial brain filled with fake blood.

These experiments implicated Von Willebrand Factor - a protein best known for stopping us from bleeding when we get a cut.

In its resting state, Mukherjee explained, Von Willebrand Factor is coiled up like a ball of string inside blood vessels, waiting for distress signals from the body that make it stretch out and start forming clots to stop bleeding.

In a brain experiencing a stroke, something else unfolds the ball.

"If there is some kind of fluid motion induced after the clot is removed, it can stretch out that ball into an extended thread that attracts platelets, forms new clots and blocks flow even after the original culprit clot is gone," Mukherjee said.

Meanwhile, the study showed, the brain's inflammatory response to stress interferes with safeguards that normally keep the protein's clotting efforts in check, creating what the authors call "a perfect storm" of collateral damage.

Other experiments, looking at blood from stroke patients at the University of Washington in St. Louis, suggest a similar phenomenon happens in humans too.

"We are the first to really show in this hyperacute phase of stroke what is happening with these cells inside blood vessels," said Denorme. "Seeing is believing."

More research is necessary to determine why no reflow happens in some stroke patients but not others. But the study did find that stroke patients with higher blood levels of a pro-inflammatory compound called Interleukin 6 had more overactive Von Willebrand Factor and worse long-term outcomes.

The researchers envision a day when therapeutics targeting Von Willebrand Factor, or the inflammatory compounds that exacerbate its clotting capabilities, could be given to stroke patients alongside clot-busting drugs and surgery.

Notably, several drugs targeting Von Willebrand Factor already exist and are approved for use for other disorders.

"It's early days. But now that we have a lead on what drives these micro-clots, we have a promising new avenue to explore for improving recovery," said Denorme.

Source:

University of Colorado at Boulder

Journal reference:

Laroche, A., et al. (2026). Mechanisms of von Willebrand factor activation driving no reflow in ischemic stroke. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.2610397123. https://www.pnas.org/doi/10.1073/pnas.2610397123

Cialis is an erectile dysfunction drug. Could it also help you live longer?

 Since the stroke already has me in the high risk category of cardiovascular disease I'm already taking Cialis daily. Better blood flow to the brain. Hasn't your doctor immediately put you on this to save some neurons from the neuronal cascade of death in the first week? 

And this:

Erectile Dysfunction Drugs May Protect Against Alzheimer’s August 2024

Cialis is an erectile dysfunction drug. Could it also help you live longer?

Tadalafil – better known by its brand name Cialis – is one of the most commonly prescribed drugs for erectile dysfunction.

But in some biohacking and wellness circles, it's increasingly being repurposed for an entirely different reason.

Online clinics and influential figures are promoting it as a kind of all-purpose longevity drug – delivering benefits for the cardiovascular system, brain and even athletic performance.

The drugs aren't approved for preventing heart attack and stroke, let alone for extending life.

However, the enthusiasm does reflect growing interest among some experts in the field of cardiology and men's health that tadalafil and other drugs in its class could have a legitimate role in preventive health.

"It's a serious area of discussion," says Dr. Robert Kloner, director of cardiovascular research at the Huntington Medical Research Institutes and a professor at the University of Southern California. 

"Cardiovascular disease remains the number one killer – and we have these drugs that may have a potential benefit, but we have to learn a lot more."

The buzz of longevity

Tadalafil belongs to the same class of drugs as sildenafil, i.e., Viagra – with the primary difference being that its effect lasts considerably longer.

While both have been on the market for decades, a handful of large studies, many of them published in recent years, have shown that men taking the drug fare better: They have lower rates of cardiovascular disease and death, and, in some cases, are less likely to develop dementia.

The major studies in this area are observational – and retrospective – meaning they can only show associations, not that tadalafil was the definitive cause.

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But the findings are remarkably "consistent" across the literature, says Kloner, whose lab has studied these medications extensively. "It's a very interesting signal."

The research has surfaced in the online longevity conversation, and prominent voices – from Stanford neuroscientist and podcaster Andrew Huberman to the immortality-seeking tech mogul Bryan Johnson – have talked up the idea of taking tadalafil for more than sex.

Even some women are getting on board.

"It seemed very harmless," says Kristi Sawicki, who holds a doctorate in molecular oncology and has built a following on social media around longevity.

"If anything it's going to help blood flow and that can be beneficial to our brain and our heart," she told NPR.

Sawicki started taking tadalafil about a year ago.

It was one of the offerings in the online telehealth clinic she used for her GLP-1 prescription. That prompted her to dig into the research herself.

"It's a very well-understood mechanism," she says.

As someone with a family history of heart disease, she saw taking tadalafil as "low-hanging fruit" for cardiovascular health – and has also noticed other benefits, like a better pump in the gym.

The studies

While mostly used for erectile dysfunction, both tadalafil and sildenafil are approved for treating a rare form of high blood pressure affecting the lungs. Tadalafil can also be prescribed for symptoms of an enlarged prostate in men.

In essence, these medications – known as PDE-5 inhibitors – work by preventing the breakdown of a signaling molecule, which in turn helps relax smooth muscle cells and dilate blood vessels.

This not only improves blood flow in one particular region but also relaxes and widens blood vessels throughout the body, Kloner says.

Sildenafil – approved in the late '90s – was famously developed as a drug to treat chest pain caused by poor blood flow to the heart, until its "side effects" were recognized and drug makers changed course.

There's evidence – mostly from small trials in humans – that PDE-5 inhibitors like tadalafil may benefit blood-vessels. Plus, lab and animal research have suggested these drugs can also have anti-inflammatory effects.

The studies drawing on medical records of men who were prescribed these drugs, primarily for erectile dysfunction, have shown sizable effects.

For example, an analysis by Kloner of more than 8,000 men taking tadalafil found they had a 55% lower rate of dying from cardiovascular causes and a 44% lower rate of overall mortality during the study period.

Another study – this based on more than half a million patients – showed a 32% lower risk of dementia among those taking tadalafil, along with improved mortality.

"We were particularly fascinated by the dementia piece," says Dr. Dietrich Jehle, chair of emergency medicine at the University of Texas Medical Branch in Galveston and lead author of the analysis, noting that data from the U.K. has also indicated a lower risk of Alzheimer's disease.

Researchers like Kloner and Jehle emphasize that without prospective studies – ideally randomized trials – these findings need to be read with caution. There could be unknown factors that influence why men who seek out medications for erectile dysfunction are less likely to die and develop certain diseases. Kloner also acknowledges the drugs are not as well studied in women.

The problem, he says, is that pharmaceutical companies aren't incentivized to run these costly studies because generic versions of the drugs are already available.

"It's not something that cardiologists are routinely recommending, I'll tell you that," Kloner says. "But these drugs in general are very safe."

The online marketplace

Much of the current marketing around tadalafil comes from direct-to-consumer online clinics, where it's often advertised alongside other trendy wellness and longevity therapies.

For example, AgelessRx – a company that Sawicki promotes in her online content – sells a monthly $70 prescription of low dose tadalafil for longevity purposes.

In an interview with NPR, the company's medical director, Dr. Jenell Decker said she felt the data were strong enough to warrant offering it to both men and women over 40.

"In longevity, that's what you have to do with a lot of things, you have to infer," she says, "because if you wait until a person is already showing symptoms, you're already behind."

But some experts are troubled by this off-label use of the medication, without better data in humans.

"Absence of evidence of harms doesn't mean there isn't harm," says Dr. Steve Nissen, chief academic officer of the Cleveland Clinic Heart, Vascular & Thoracic Institute. "In the absence of randomized controlled trial data, it's pretty hard to justify."

Expert panel evaluating the merits

There are signs tadalafil could be gaining wider acceptance outside of the online wellness and optimization world.

The topic came up recently during the latest meeting of an influential medical group, known as the Princeton Consensus Panel, which focuses on men's sexual function and cardiovascular health.

The group of medical experts – which included Kloner and other preventive cardiologists – arrived at consensus language that low dose tadalafil is "appropriate" for a subset of men who are at elevated risk of developing cardiovascular disease due to the build up of plaque in their arteries, according to Dr. Martin Miner, who co-chaired the June conference. (Their formal recommendations are not yet published.)

In an email to NPR, Miner acknowledged some were "hesitant" to endorse this broader use of tadalafil because there were no randomized controlled trials, but ultimately decided to do so, based on the existing observational research.

"This is not for all men," says Miner, who directs the Men's Health Center at Brown University in Providence, R.I., though he does prescribe it for many of his patients who're at higher risk of cardiovascular disease.

"I believe men need all the help we can give them due to the longevity gap in this country," he added.