The University of Southampton

Author: Millie Milkins

Bridge to Recovery: Stem Cell-Studded Scaffolding in Stroke Rehabilitation

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Despite 100,000 people experiencing a stroke each year in the UK alone and statistically one in four people over the age of 25 having a stroke in their lifetime, there is currently no clinically effective treatment available to reverse the brain damage caused by strokes.

Last summer my mother had a stroke. Not long ago, this sentence filled me with both sadness and fear of what this actually meant, something not only I was feeling. The road to recovery for stroke patients can be steep and unknown due to the short time treatment can be given within, and the limited options currently available. This led my opinion of stroke research to be pretty negative and views of progress to be at a standstill.

A stroke is a life-threatening condition that occurs when the blood supply to parts of the brain is cut off, this lack of blood means no oxygen and nutrients can reach the brain leading to cell death. Strokes are medical emergencies, however, if caught early and treated patients are more likely to make a full recovery with almost no permanent disabilities.

The current treatments available in the UK depend on whether the stroke was ischemic; when blood supply to a region of the brain is blocked, or haemorrhagic; when there is excessive bleeding in parts of the brain. Other factors also include the time since the symptoms began and the presence of any other medical conditions.

Roughly 87% of all strokes are ischemic!

Treatments for an ischemic stroke include both medical procedures and medications. Mainly a medicine called a tissue plasminogen activator is used, which breaks up the blood clots that are restricting flow to the brain.

Whereas, for a haemorrhagic stroke blood pressure medicines are normally prescribed to lower the pressure on blood vessels alongside some form of procedure such as aneurysm clipping, coil embolisation, draining excess fluid and surgery to temporarily remove part of the skull.

Although there are multiple treatments available none are specifically tailored to each patient and can specifically target damaged areas regardless of the time taken to receive care. So, what if there was a way to precisely target damage no matter how long after the initial stroke?

A New Potential Delivery System…

In 2018, the University of Minnesota McAlpine research group projects 3D-printed a neuronal spinal cord scaffold.

Recent studies by Baker (2009) and Bible et al. (2009) aimed to develop technology for stem cell delivery to treat brain damage. They successfully attached neural stem cells to scaffold particles, optimised conditions for cell viability, determined the ideal particle size for effective delivery, and used MRI-guided implantation for precise targeting. Observations showed primitive tissue formation within seven days post-implantation, marking significant progress in developing stem cell scaffold matrices for stroke treatment. The study highlighted the potential of stem cell research to enhance transplantation viability using bio-scaffolding.


Researchers implanted neural stem cell-coated polymer particles into rat brains with simulated strokes using MRI-guided needles. Some cells formed a fibrous web within the graft, relying on blood vessel support for long-term survival. Post-mortem MRI images highlighted the grafted area, showing new tissue growth in green fluorescence.

Delving into stroke research has been an eye-opening journey for me, exploring the complex world of neurological damage and potential new treatments. It’s captivating to realise the immense challenges faced by individuals like my mother and other stroke survivors including the impacts on their lives and families, all adding to the urgent need for effective treatments. Investigating the latest developments in stem cell therapy, tissue engineering, and imaging techniques has left me both impressed and inspired for the future of stroke therapeutics.

New Stealthy Stem Cells?

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Developments in new gene editing techniques provides stem cells with the ability to bypass the immune system offering new applications in cell replacement therapy.

There are more than 10 million people worldwide currently living with Parkinson’s disease and 3 million people recorded to be living with type 1 diabetes globally in 2017. Both of these chronic diseases are currently incurable and require regular medication and treatment to control. Due to their life-long impacts, many people can relate to the implications these diseases have on both the individuals diagnosed and the family members or friends of the individuals. The negative effects can be physical, mental, social or financial and often a collection of them all.

So if there was a possible solution would you take it?

Research has suggested a new strategy that could provide an endless supply of replacement body parts for individuals suffering from debilitating disorders and diseases. Scientists can now grow stem cells in the laboratory and engineer them into specialised cell types. Which can eventually be transplanted into humans and potentially cure diseases, once believed to be incurable. For Parkinson’s disease this could mean cultivating neurones to combat the progressive damage made by the disease over the years to different parts of the brain, or for type 1 diabetes insulin-producing pancreatic cells could completely reverse the effects of the disease and lastly heart muscle cells to could be transplanted to enhance cardiac function. These are just a few examples of the life-changing effects this new treatment could have.

In genetically modified mice predisposed to autoimmune diabetes, pancreatic cells undergo infiltration and destruction by “killer” T-cells, leading to a decline in insulin production (pictured on the left). However, administration of MOTS-c injections mitigated T-cell infiltration, consequently averting disease onset (pictured on the right).

Credit: Newcomb (2021)

How this is possible…

Utilising gene-editing techniques like CRISPR-Cas systems, stem cells can be manipulated to possess immune-evading traits, effectively bypassing recognition mechanisms. Moreover, these engineered cells can integrate fail-safe features to guarantee cells can be eliminated in the case of unforeseen issues. Consequently, such ‘stealth’ cells hold promise to support various cell-replacement therapies.
In most cases, the process starts with the disruption of at least one component of the cell’s major histocompatibility complex (MHC). This complex functions like a molecular identity card, showcasing distinct cellular information fragments that inform the immune system’s T lymphocytes, its frontline defenders, and whether the cell is hostile.
To mitigate potential susceptibility to natural killer cells (NK), certain researchers have suggested the reintroduction of genes encoding particular MHC antigens. These antigens enable the cell to modulate NK cells without eliciting T-cell responses that may induce apoptosis (cell death). NK cells serve as the effector lymphocytes of the innate immune system, tasked with regulating various tumour types and microbial infections to restrict their dissemination and consequent tissue harm. Alternatively, other strategies may involve introducing genes that produce ‘checkpoint’ proteins, specialised molecules aimed at directly suppressing NK cell activity.

Are there any downfalls to this ground-breaking new strategy?

Unfortunately, therapies stemming from stem cells require customisation for each patient, a process that is both time-consuming and costly. Alternatively, these treatments can utilise donor cells; however, due to the tendency of the immune system to reject foreign cells, such ‘allogeneic’ therapies require the administration of immune-suppressing medications alongside treatment. However, this approach escalates the risk of complications like infection and cancer.

Ultimately, the optimal safety strategy, as well as the ideal extent of gene editing required to suppress immune responses, may vary depending on the disease. For instance, pre-made cell therapy for cancer may not require the same design features as one tailored for diabetes, given the differences in the immune system’s response and the distinct risk-benefit considerations for each ailment. In essence, there is no ‘one-size-fits-all’ solution.

With the true test of human trials likely to follow soon the future of this treatment is looking hopeful.

Acknowledgements:

Dolgin, E. (2024). Stealthy Stem Cells to Treat Disease. Nature. [online] doi:https://doi.org/10.1038/d41586-024-00590-y.

Green, A. (2008). Descriptive Epidemiology of Type 1 Diabetes in Youth: Incidence, Mortality, Prevalence, and Secular Trends. Endocrine Research, 33(1-2), pp.1–15. doi:https://doi.org/10.1080/07435800802079924.

Newcomb, B. (2021). Small Protein Protects Pancreatic Cells in Model of Type 1 Diabetes. [online] USC Leonard Davis School of Gerontology. Available at: https://gero.usc.edu/2021/08/12/mots-c-mitochondria-type-1-diabetes/ [Accessed 5 Mar. 2024].

Parkinson’s Foundation (2024). Statistics | Parkinson’s Foundation. [online] www.parkinson.org. Available at: https://www.parkinson.org/understanding-parkinsons/statistics#:~:text=Parkinson.

Vivier, E., Tomasello, E., Baratin, M., Walzer, T. and Ugolini, S. (2008). Functions of Natural Killer Cells. Nature Immunology, 9(5), pp.503–510. doi:https://doi.org/10.1038/ni1582.