Stem cells are heterogeneous cell populations, meaning they have various and different properties rather than being alike. They are often mistakenly considered capable of repairing almost every tissue, because of their capacity to differentiate into cells of every tissue type. Based on these expectations, stem cells have been proposed as a source of cells for tissue repair in different areas of regenerative medicine, including neurology.
T and B cells are elements of the body’s immune system, also known as lymphocytes. Both types of cells perform a role when the body is under attack: B cells produce antibodies and T cells mobilise other cells as part of the immune response. In MS the body orchestrates a faulty immune response. Autoreactive T and B cells in the CNS recognise the body’s own myelin antigens as foreign bodies, attacking and destroying the myelin. Breakdown of myelin (demyelination) leads to impairment of nerve conduction and, in the long run, neuronal damage, the biological basis of irreversible disability. The ideal treatment for MS should therefore target the autoreactive cells, protect the assaulted CNS tissue and promote its repair.
Recent studies conducted in experimental autoimmune encephalomyelitis (EAE), the animal disease that resembles MS, have demonstrated that mesenchymal stem cells (MSCs) may be able to achieve some of these goals.
MSCs were first characterised in the bone marrow where they form cellular components in the blood through closely interacting with haematopoietic stem cells (HSCs). The natural pathway of MSCs is differentiation toward tissues such as bone, joint, fat, muscle and tendons, referred to as mesodermal tissues. Based on their natural tendency, MSCs might be better considered as multipotent precursor cells of mesodermal tissues, rather than true stem cells. However, under specific experimental conditions, MSCs have the ability to differentiate into other cell types including neural cells. More recently, studies have demonstrated that MSCs can affect many functions of cells of the immune system including activated T and B cells. In the presence of MSCs, lymphocytes and other immune cells do not increase in number and cannot produce the inflammatory cytokines – signallers of the faulty immune attack. Based on the capacity of MSCs to adjust the immune response and their apparent ability to differentiate into neural cells, MSCs were tested as treatment of EAE. Intravenous injection of MSCs in mice with EAE led to a striking improvement in the clinical course of the disease and reduced inflammation and demyelination.
| This beneficial effect was obtained when the mice were treated early after disease onset and was associated with moderating the T and B cell response against myelin antigens detected in the lymph nodes, suggesting the possibility that MSCs may be able to modulate the autoimmune attack against myelin. In contrast, clinical improvement was not seen in mice treated after the disease had reached the chronic phase. Injected MSCs could be detected inside the inflamed CNS, but without any significant evidence of them changing into neural cells. However, less axonal loss associated with an increased number of neurons in the inflamed areas of the CNS was observed. A protective effect on neurons and other cell types exposed to inflammatory and other toxic threats has also been demonstrated in a controlled environment (in vitro) and in animal experiments, suggesting that MSCs could foster the survival of injured or dying cells in a living organism (in vivo).
As MS is a disease where neural degeneration follows CNS inflammation and demyelination, these results suggest MSCs could be a potential treatment for MS. However, there is no evidence so far that MSCs could become an effective therapy for patients with severe disability due to chronic and irreversible neural loss. In this situation it is not known whether MSCs, or any adult stem cell, could regenerate the complex neural network needed to recover from severe impairment. Current experimental evidence indicates that this possibility is, unfortunately, unlikely.
Despite these concerns, the use of MSCs for the treatment of MS is possible and not some futuristic concept. Indeed, MSCs have been obtained for clinical purposes through bone biopsy or through aspirating fatty tissue. Although the long-term safety of injected MSCs is still unknown, they have been used to foster the development of blood cells (haematopoiesis) upon bone marrow transplantation from a non-compatible donor (a donor with a different blood type than the recipient) and as therapy for the treatment of a limited number of acute diseases including heart failure and graft-versus-host-disease (GVHD).
Thus, based on data from animals with EAE and clinical experience gained from other diseases, MSCs may represent a future therapy for the treatment of people with rapidly worsening MS, in whom currently available therapies are not effective. Future studies must verify MSCs’ capacity to differentiate into neural cells in vivo and possibly the promotion of endogenous recovery by local neural precursor cells, which support axons and produce the myelin sheath, thus providing hope for tissue repair and regeneration.
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