Potential New Treatment for Multiple Sclerosis Sufferers -Their Own Skin Cells
Diagram shows a neuronal cell sheathed by an oligodendrocyte.
Scientists have shown in mice that skin cells re-programmed into brain stem cells, transplanted into the central nervous system, help reduce inflammation and may be able to help repair damage caused by multiple sclerosis (MS).
The study, led by researchers at the University of Cambridge, is a step towards developing personalised treatments based on a patient’s own skin cells for diseases of the central nervous system (CNS).
In MS, the body’s own immune system attacks and damages myelin, the protective sheath around nerve fibres, causing disruption to messages sent around the brain and spinal cord. Symptoms are unpredictable and include problems with mobility and balance, pain, and severe fatigue.
Key immune cells involved in causing this damage are macrophages (literally ‘big eaters’), which ordinarily serve to attack and rid the body of unwanted intruders. A particular type of macrophage known as microglia are found throughout the brain and spinal cord – in progressive forms of MS, they attack the CNS, causing chronic inflammation and damage to nerve cells.
Recent advances have raised expectations that diseases of the CNS may be improved by the use of stem cell therapies. Stem cells are the body’s ‘master cells’, which can develop into almost any type of cell within the body. Previous work from the Cambridge team has shown that transplanting neural stem cells (NSCs) – stem cells that are part-way to developing into nerve cells – reduces inflammation and can help the injured CNS heal.
However, even if such a therapy could be developed, it would be hindered by the fact that such NSCs are sourced from embryos and therefore cannot be obtained in large enough quantities. Also, there is a risk that the body will see them as an alien invader, triggering an immune response to destroy them.
A possible solution to this problem would be the use of so-called ‘induced neural stem cells (iNSCs)’ – these cells can be generated by taking an adult’s skin cells and ‘re-programming’ them back to become neural stem cells. As these iNSCs would be the patient’s own, they are less likely to trigger an immune response.
Now, in research published in the journal Cell Stem Cell, researchers at the University of Cambridge have shown that iNSCs may be a viable option to repairing some of the damage caused by MS.
Using mice that had been manipulated to develop MS, the researchers discovered that chronic MS leads to significantly increased levels of succinate, a small metabolite that sends signals to macrophages and microglia, tricking them into causing inflammation, but only in cerebrospinal fluid, not in the peripheral blood.
Transplanting NSCs and iNSCs directly into the cerebrospinal fluid reduces the amount of succinate, reprogramming the macrophages and microglia – in essence, turning ‘bad’ immune cells ‘good’. This leads to a decrease in inflammation and subsequent secondary damage to the brain and spinal cord.
“Our mouse study suggests that using a patient’s reprogrammed cells could provide a route to personalised treatment of chronic inflammatory diseases, including progressive forms of MS,” says Dr Stefano Pluchino, lead author of the study from the Department of Clinical Neurosciences at the University of Cambridge.
“This is particularly promising as these cells should be more readily obtainable than conventional neural stem cells and would not carry the risk of an adverse immune response.”
The research team was led by Dr Pluchino, together with Dr Christian Frezza from the MRC Cancer Unit at the University of Cambridge, and brought together researchers from several university departments.
Dr Luca Peruzzotti-Jametti, the first author of the study and a Wellcome Trust Research Training Fellow, says: “We made this discovery by bringing together researchers from diverse fields including regenerative medicine, cancer, mitochondrial biology, inflammation and stroke and cellular reprogramming. Without this multidisciplinary collaboration, many of these insights would not have been possible."
This article has been republished from materials provided by Cambridge University. Note: material may have been edited for length and content. For further information, please contact the cited source.
Peruzzotti-Jametti, L et al. Macrophage-derived extracellular succinate licenses neural stem cells to suppress chronic neuroinflammation. Cell Stem Cell; 2018; 22: 1-14; DOI: 10.1016/j.stem.2018.01.20
Inter-areal Balanced Amplification Enhances Signal Propagation in the BrainNews
Neuroscientists find that signal transmission in a large-scale model of the primate brain is robust under the condition in which area-to-area connections exhibit a “balance” between excitation and inhibition.READ MORE
Early Life Experiences Alter DNA Structure in the Adult BrainNews
Scientists report in the journal Science that the type of mothering a female mouse provides her pups actually changes their DNA.READ MORE
Worms Exhibit Fear and Respond to Anti-anxiety MedsNews
A team of investigators has uncovered new clues about the mechanisms of fear and anxiety through an unlikely creature: the tiny nematode worm.READ MORE
Comments | 1 ADD COMMENT
Sorice Madina | Mar 18, 2018
I was diagnosed with multiple sclerosis in 95 but had my first symptoms in 87. I tried Betaseron for about 6 years or so. In 2012 I went to a care facility, life was too difficult at home for my husband and family. I have tried several types of medications. I thought you just have to let it run its course; both my legs were spasming mostly at night which makes sleeping difficult.My multiple sclerosis got significantly worse and unbearable because of my cognitive thinking.. I lost touch with reality. Last year I started on the Multiple Sclerosis natural herbal formula we ordered from GREEN HOUSE HERBAL CLINIC, We spoke to few people who used the treatment here in Canada and they all gave a positive response, my symptoms totally declined over a 7 weeks use of the Green House multiple Sclerosis disease natural herbal formula. I am now almost 73 and doing very well, the disease is totally reversed! (Visit their website www . Greenhouseherbalclinic . com) I am thankful to nature, herbs are truly gift from God. I will keep sharing more awareness, Share with friends!!
International Conference on Neuroimmunology, Neurological disorders and Neurogenetics
Sep 26 - Sep 27, 2018