ROLE OF STEM CELL THERAPY FOR MULTIPLE SCLEROSIS
What is Multiple Sclerosis?
Multiple Sclerosis (MS) is an autoimmune and neuro-degenerative disease of the central nervous system (CNS). In autoimmune etiology, there is a prevailing theory in which oligodendrocytes are believed to be permanently damaged by CD4+ T-cells, CD8+ T-cells, and macrophages.
In MS patients, auto-reactive CD4 T-cell penetration of the CNS leads to myelin injury and inflammatory responses and scarring of white matter, which can lead to severe disability and neurological defects. MS progression following demyelination typically pursues one of four courses,
- Relapsing-remitting MS (RRMS)
- Secondary progressive MS (SPMS)
- Primary progressive MS (PPMS) and,
- Progressive-relapsing MS (PRMS)
To date, the effectiveness of disease-modifying drugs has been approved only in a limited number of MS patients, especially in the relapsing forms of PRMS.
Advent of Stem cells as a therapeutic agent for patients with MS
Stem cells (SCs) have uncovered a new perspective as therapeutic tools in neurological disorders such as MS. These cells are pluripotent cells with a capacity to give rise to different cell types, that are infinite sources of neurons and glia for therapies aimed at cell replacement or neuro-protection in disorders affecting the brain and spinal cord like MS.
The two main stem cell types are embryonic stem cells (ESCs) and adult stem cells.
ESCs are formed four to five days after fertilization from the inner cell mass of the blastocytes with an ability for unlimited growth in culture that could be related to a high risk of teratoma formation. Adult stem cells are specialized cells including,
• Hematopoietic stem cells (HSCs)
• Mesenchymal stem cells (MSCs) and,
• Neural stem cells (NSCs)
1) Mesenchymal stem cell (MSC) therapy
Mesenchymal stem cells are self-replicating cells that are capable of differentiating in multidirectional pathways, such as, osteoblasts, chondrocytes, myocytes, marrow stromal cells, tendon-ligament fibroblasts, adipocytes, and neural cells. While a routine source of human MSCs is the bone marrow, they have been also derived from multiple adult tissues comprising of adipose tissue, umbilical cord blood, placenta, thymus, and dental pulp.
Transplanted MSCs not only directly differentiate into neurons and endothelial cells after induction, but also, it is surely believed, that their secretome can mediate their valuable actions. Several autocrine/paracrine factors could be secreted from MSCs that have many benefits.
Routes of administration of mesenchymal stem cells,
• Intrathecal injection
• Autologous intravenous (IV) MSC therapy
2) Hematopoietic stem cell (HSC) therapy
Hematopoietic stem cells are found chiefly within bone marrow in niches created by surrounding stromal cells. HSCs have the potential to differentiate into the main hemato- and lymphopoietic precursors, which then differentiate into mature cells. They are generated in large numbers throughout human life and continually repopulate blood and immune systems.
The sources of HSCs are bone marrow, peripheral blood, umbilical cord blood, fetal hematopoietic system, ESCs and embryonic germ cells.
Modes of administration of Hematopoietic stem cells,
• Autologous – immune system is wiped out by reinfusion of the patient’s own HSCs
3) Neural stem cell (NSC) therapy
Neural stem cells are defined as self-renewing multipotent progenitors existing in the developing and adult CNS. Generally, they are considered by their capacity to symmetrically self-renew and their ability to discriminate into neurons, oligodendrocytes, and astrocytes through asymmetrical fate- committed division.
Routes of administration of Neural stem cells,
On the basis of the published evidence, to date, SC transplantation can be regarded as a potential source of treatment for MS. It can be concluded that the availability of HSCs and MSCs are more than NSCs, but still NSCs which have the unique feature of beneficial effects with remyelination make it attractive for further studies in clinical stages to see whether they show this benefit in practice, particularly in the progressive stages of MS.