Autologous mesenchymal stem cells, commonly called MSCs, have been shown to induce immunologic and neurologic effects (neuroregenerative and neuroprotective) in animal models. Autologous transplant means that the cells are taken from then re-injected into the same subject.
Under the right conditions, animal studies have shown that MSCs can mature into myelin-producing cells in MS disease models. Myelin is important because MS is characterized by damage to the myelin sheath, a protective covering that surrounds the nerves of the central nervous system.
Adipose-derived stem cells (ASC) are adult MSCs taken from fat. They can be isolated through enzymatic digestion. MSCs are also found in bone marrow, skin, and other body parts.
Mesenchymal Stem Cell Studies
A recent study evaluated the safety and tolerability of intrathecal (injected into the spine) autologous transplant of adipose stem cells over one year. The secondary objectives were relapse rate and progression of the disability which were assessed 18 months after the study began. Researchers aimed to achieve local immunomodulation (return) of the participant’s immune system via transplantation of autologous ASCs.
Results of the study suggested that ASC intrathecal therapy for MS is safe and slows the progression of the disease. The method may benefit people with rapidly progressive MS because it is a powerful anti-inflammatory and immunosuppressive treatment. No differences in the Expanded Disability Status Scale (EDSS) score were found in the 18 month-period between groups of relapsing-remitting and slow progressing MS participants. No disease progression occurred among participants by the end of the study follow-up. No serious or severe adverse effects were observed. Time without progression of the disease was 18 months for most participants.
ASCs are promising candidates for cell-based therapies aimed at stopping and reversing the loss of myelin in MS patients, but ACSs should be reserved for aggressive cases, for disease still in the inflammatory phase, and for the rare malignant form of the disease.
Bone marrow-MSCs were intrathecally administered in another study. The study showed that the treatment was safe and well tolerated in people with MS and that no adverse events occurred.
Another recently published study demonstrated that damaging immune system defects seen in patients with multiple sclerosis (MS) may be repaired using umbilical-cord MSCs.
Note: Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
- https://www.hindawi.com/journals/mi/2016/5302120/
- http://www.neurology.org/content/84/14_Supplement/P7.200
- http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=12345&path%5B%5D=39106
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Stem Cell Combo Therapy Shows Efficacy in MS Mouse Model, Korean Study Shows
A combination therapy of low-dose methylprednisolone and interferon (IFN)-beta-secreting stem cells is effective in a mouse model of multiple sclerosis (MS), a new Korean study suggests.
The research, “Effective combination of methylprednisolone and interferon β-secreting mesenchymal stem cells in a model of multiple sclerosis,” appeared in the Journal of Neuroimmunology.
Doctors often prescribe methylprednisolone, a corticosteroid used to suppress the immune system and decrease inflammation, to MS patients. However, high doses over a long period are inconvenient and costly. They may cause side effects including weight gain and decreased resistance to infection, as well as hyperglycemia (high levels of glucose in the blood).
In a mouse model of MS known as the experimental autoimmune encephalomyelitis (EAE) mouse, methylprednisolone suppressed disease activity and progression. However, combining low-dose methylprednisolone with other drugs also reduced clinical severity in mice, suggesting that new formulations may decrease MS severity while avoiding the side effects of high-dose methylprednisolone.
IFN-beta, an approved therapy for MS, has potent anti-inflammatory and immunomodulatory effects. Yet its short half-life — the period of time over which the concentration of the drug in the body falls by half — hampers its therapeutic efficacy. IFN-beta’s inability to cross the blood-brain barrier and reach the central nervous system is also a disadvantage.
The research team at Seoul’s Catholic University of Korea previously showed that IFN-beta-secreting mesenchymal stem cells (MSCs-IFN-beta) derived from human bone marrow reduce the severity of MS and in EAE mice. Specifically, stem-cell treatment decreased inflammatory cell infiltration, mitigated the loss of myelin and promoted anti-inflammatory effects.
MS symptoms and pathological mechanisms are complex. For this reason, combination therapies targeting multiple disease aspects could provide significant therapeutic benefit.
In the latest study, investigators assessed whether combining low-dose methylprednisolone and MSCs-IFNβ could offer more therapeutic benefits to EAE mice than either therapy alone.
Results showed that the combo treatment decreased disease severity and inflammatory cell infiltration, and helped repair the myelin sheath. In addition, the combo treatment reduced disruption of the blood-brain barrier as well as reactivation and death of T-cells, a type of immune cell involved in MS development.
Overall, the study shows “for the first time that a combined treatment consisting of MP [methylprednisolone ] and MSCs-IFN[-beta] has enhanced therapeutic efficacy compared with each treatment individually. These results provide invaluable insight into the potential of combined treatments with standard MS drugs and may offer new therapeutic options for treating patients with MS.”
Myelin-producing Brain Cells Regenerated Using Stem Cells in Early Study
Researchers, using two different kinds of stem cells in rats, were able to regenerate oligodendrocytes — myelin-producing brain cells that are defective in multiple sclerosis (MS). They were also able to grow adult neural stem cells in laboratory cultures and prod them to develop into oligodendrocytes.
The exact cause of MS is unknown — including what triggers attacks on myelin — but the loss of oligodendrocytes seen in the disease is known to play a role in its progression.
Nerve cells in the brain send their signals through their axons, long arm-like structures that extend out from the centers of the nerve cells. The signals are electrical pulses transmitted along the length of an axon. Oligodendrocytes provide the insulation — called myelin — that wraps around axons, speeding up the transmission of electrical signals through the nerve cells.
Loss or malfunction of oligodendrocytes means that signaling in the brain is impaired. It is this slowing of signaling that is thought to cause MS symptoms.
Researchers from the Heinrich-Heine-University, Germany, with support from British and Chilean colleagues, designed a novel approach to regenerate oligodendrocytes, according to a press release.
Stem cells are immature cells that give rise to differentiated cells — cells with a specific function, such as oligodendrocytes.
Adult neural stem cells can divide and produce nerve cells and other brain cells, including oligodendrocytes. However, in normal circumstances, the regeneration of cells that take place in the human brain is not enough to repair the damage seen in MS.
The researchers set out to find conditions that would promote the differentiation of adult human NSCs into oligodendrocytes. They discovered that another type of stem cell, mesenchymal stem cells (MSCs), could provide the signals required.
First they tested their system in rats, and found that by using factors produced by human MSCs, they could induce the growth of new oligodendrocytes in the animals.
Then they grew adult NSCs in the laboratory, and using the same factors from human MSCs were able to promote the establishment of oligodendrocytes in the cultured cells.