Stem Cell Therapy for Stroke: Progress and Challenges
Post by Shahin Khodaei
What's the science?
A stroke is a serious medical condition where blood flow to a part of the brain is reduced, causing the death of brain cells and impairments in movement, speech, or cognition in survivors. The majority of strokes are ischemic strokes, meaning that blood supply is disrupted because of a blockage in blood vessels. Currently, the only FDA-approved treatments for ischemic stroke involve removing the blockage either mechanically or pharmacologically to restore normal blood supply, however, this treatment is only effective within a few hours of the stroke onset. Finding new treatments that can be effective at later time points is critical. This week in Brain, Rust and colleagues published a review paper on one such treatment strategy: stem cell therapy for long-term treatment of ischemic stroke.
What happens in ischemic stroke?
When blood supply to a brain region is interrupted, millions of neurons and billions of synapses quickly die. Beyond the damage to neurons, stroke causes massive local and systemic inflammation and significant damage to the blood-brain barrier (BBB), which regulates what substances enter and exit the brain. These changes all have lasting negative consequences on brain function. Over the subsequent days and weeks, neurons can also die off in distant brain regions anatomically connected to the stroke site.
After a stroke, the brain’s built-in neuroplasticity processes kick in. Some new neurons and synapses may be created, and surviving brain regions start to take on some of the functions of the brain areas lost in the stroke. In addition, new blood vessels form around the site of the stroke, and the support cells in the brain are able to partially restore the BBB. All these mechanisms lead to some degree of functional recovery in patients – this plasticity window peaks during the first 3 months and gradually weakens 6-12 months after stroke.
How can stem cell therapy help?
Given that many neurons die in a stroke, a treatment strategy that replaces the lost cells using stem cells is an intuitive concept. Preclinical studies using animal models have shown that using stem cells after stroke may be therapeutic in two ways. One is the replacement of lost cells, where stem cells turn into brain cells and integrate into the existing neuronal networks to restore function. However, this form of direct integration is rather limited, because newly formed neurons and cells often have a short lifespan. Instead, emerging studies show that transplanted stem cells support the brain’s built-in plasticity processes, leading to beneficial effects. These include reducing the massive inflammatory response that follows a stroke, the repair and remodeling of blood vessels, and the repair of neural circuits. Both cell replacement and support processes were reported following stem cell transplant in a recent preclinical study by Rust’s team. Using a mouse model, transplanting cells 7 days after stroke caused increased neuronal plasticity, blood vessel repair and remodeling, and improved motor function. These transplanted cells developed into neurons and other brain cells that survived for at least five weeks and cross-talked with surrounding stroke tissue to activate plasticity and regeneration processes.
Clinical trials using stem cells after stroke started two decades ago, and have shown that this approach is safe, without significant negative effects. However, in terms of effectiveness, these clinical trials have found mixed results. Rust and colleagues suggest that findings from preclinical studies can teach us how to more effectively use stem cells in a clinical setting. For example, to increase the lifespan of stem cells, preclinical studies have treated the cells pharmacologically and genetically before transplanting them into the brain – a similar approach may be used in clinical trials in the future to possibly increase the effectiveness of stem cell therapy.
What's the bottom line?
Stem cell therapies have been recognized as one of the most promising approaches to help survivors of stroke. Unfortunately, clinical trials using this strategy have not shown consistent improvements for patients thus far. Rust and colleagues argue that our growing understanding of the mechanisms of stem cell therapy from preclinical studies can help improve the effectiveness of this approach for patients, ultimately leading to better treatment for stroke.