Multiple Sclerosis (MS) is a chronic autoimmune disease impacting the central nervous system (CNS) distinguished through primary demyelination and a variable extent of axonal loss 7 . MS is caused by the existence of several merging demyelinated lesions in the grey and white matter of the CNS which is also present in the cortex and brain stem as shown in the MRI (Magnetic Resonance Imaging) of Figure 1 7 . The progression of MS is exceedingly variable and unexpected as most patients experience transient neurological abnormalities at first followed by gradual neurological deterioration 5 . MS is diagnosed based on tests carried out by a neurologist through the observation of a person’s symptoms (checking movement, balance, or vision) or from pictures obtained by a magnetic resonance imaging (MRI) of the brain. An MRI monitors the quantity of water in the body 12 . Due to various areas of the brain containing varying amounts of water, the MRI can differentiate them and create images of the central nervous system 12 . The protective myelin covering is fatty and repels water. This implies that we can assess the amount of myelin present since it appears differently on a scan than nerves and other brain cells 12 .
Figure 1: MRI scans comparing brain of a person with and without MS 3 .
Additionally, MS has no established origin although it appears to be caused by a combination of genetic predisposition and non-genetic triggers such as viruses or environmental factors which results in recurring immunological attacks on the CNS 5 . Although MS is not inherited, people with relatives containing the disease are more susceptible of having this disease. The genes linked to the predisposition are HLA-DRB1 locus in the class II region. Furthermore, earlier studies regarding the heredity of MS had revealed a recurring relative risk for siblings 1 . The possibility of MS is significantly increased when both parents have MS, but the probability of half siblings is lower than that of full siblings being affected by MS 11 . Therefore, the chance of MS recurrence increases in proportion to the amount of genetic sharing with the afflicted family member but not in a liner manner 11 . A review of over 500 research revealed that there was a recurrence rate of 18.2% for monozygotic twins and 2.7% for siblings 11 .
Stem cell technologies have been investigated in reducing the progression of aggressive multiple sclerosis. The main ones being autologous haematopoietic stem cell transplantation (aHSCT) and mesenchymal cell therapy (MCT). aHSCT, often referred to as a bone marrow transplant, involves the removal of a person’s immune system cell then regrowing it using haematopoietic stem cell which develop into different types of blood cells such as red or white blood cells 13 . Thus, aHSCT infusions enhance bone marrow healing and immunological regeneration, aiming to avoid the progression of neurological impairments 9 . This potentially strengthens neurological function as well as containing numerous benefits, it aids bone marrow function by 'rebooting' the body's immune system via renewal and re-diversification of the T and B-cell repertoire, as well as heightened regulatory T-cell activity 14 . In a prospective investigation of MS patients who underwent aHSCT, over half lived without neurological deterioration for 5 years following the transplant 9 . Additionally, it generates functional cells that replace dysfunctional nerve cells in diseases other than MS such as immune deficiency syndromes 6 . From the beginning to numerous weeks after the procedure, the patient requires monitoring and additional treatments. In recent times, improvements to AHSCT process have resulted in a reduction in treatment-related mortality (TRM) from 7.3% to less than 0.5% 8 . Fifty percent of patients treated with aHSCT recovered from their condition after ten years 8 .
MCT involves eliminating a person’s MCT from their bone marrow or tissue which is multiplied in a laboratory then numerous MCT are re-introduced 13 . MCT has emerged as a possibly safe cellular treatment for MS however the dosage, method, and administration must be examined and further quantified 4 . Stem cells are similar to tumour cells in certain ways because of their capacity to proliferate for an extended length of time, high vitality, and resistance to apoptosis 10 . Their ability to proliferate for pro longed amount of time is dependent on their ability of dividing. Patients who are transplanted with stem cells frequently have long-term chemotherapy or radiation, so their immune system does not perform correctly, which can also relate to the risk of tumorigenesis 10 . Effects of chemotherapy include constant fatigue, being sick and increased risks of infections.
Whereas, the aHSCT technique has been found to provide long term sustained emission but also requires more research to determine the conditioning plan to be implemented 4 . More research is required due to increased risk of infection due to immunodeficiency which are current concerns of aHSCT as well as associations of rare cases of death. As aHSCT can cause residual cancer and requires a donor that is suitable, fitting to the recipient, they are the current focus of research 2 . Whereas for MCT, the current focus for research is finding a way to ease the side effects which include fever, headaches, and urinary tract infection.
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