A study conducted by scientists from the University of Cambridge, UK, demonstrated that transplantation of brain stem cells derived from reprogrammed skin cells helps to reduce inflammation and repair damage caused by multiple sclerosis. The results, published on February 22, 2018 in Cell Stem Cell, are an important step in the development of individual treatment of central nervous system (CNS) diseases based on the patient’s autologous cells.
In multiple sclerosis (MS),
the body’s own immune system attacks and destroys myelin, the protective sheath around nerve fibers, causing disruption to messages sent around the brain and spinal cord. In the end, nerves themselves are irreversibly damaged. Symptoms of the disease are unpredictable and include problems with mobility and balance, pain, and severe fatigue.
Key immune cells involved in in causing this process are macrophages, whose role is
usually to capture and digest foreign and toxic particles or cell debris in the body. In progressive forms of MS, a certain type of macrophage located in the brain and spinal cord, and known as microglia, attacks the central nervous system, causing chronic inflammation and damage to nerve cells.
The successful development of cell therapy around the world gives hope for an improvement in the condition of patients with CNS diseases due to stem cell (SC) treatment.
Stem cells –
universal cells, which can be converted into virtually any type of body cells. Previous work team from Cambridge showed that transplantation of neural stem cells (NSC), differentiating into neurons, reduces inflammation and helps restore the damage to the central nervous system.
However, even with successful development of such therapy, the main disadvantage is that usually NSCs are obtained from embryos, and this significantly limits their number. In addition, there is a risk that the body will see them as an foreign invader, triggering an immune response to destroy them.
The solution to this problem would be the use of induced neural stem cells (iNSCs), which can be obtained by reprogramming adult mature skin cells. As these iNSCs would be the patient’s own cells, they are less likely to trigger an immune response.
In this study, scientists from Cambridge have shown that iNSCs may be a viable option for restoring some of the injuries caused by multiple sclerosis.
Using a special line of mice with MS, the researchers found that chronic multiple sclerosis leads to a significantly increased levels of succinate (sodium succinic acid salt), a natural metabolite formed in the process of oxidative degradation. Succinate causes inflammation, sending “false” signals to macrophages and microglia in the cerebrospinal fluid, but not in the peripheral blood.
Transplanting stem cells
and iNSCs directly into the cerebrospinal fluid reduces the amount of succinate, reprogramming the macrophages and microglia, turning “bad” immune cells into “good” ones. This leads to a reduction in inflammation and a decrease in the level of 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.”