Hematopoietic Stem Cell Transplants May Provide Long-Term Benefit for People with MS
- intense immunosuppression followed by a hematopoietic stem cell transplant may prevent disability associated with multiple sclerosis (MS).
- Stem Cell Enhancers can stimulate BMSC mobilisation with milder side effects, and long-term usage can result in significant nerve repair, including MS benefits.
Multiple sclerosis is a chronic inflammatory disease that affects the central nervous system. It is characterised by demyelination, axonal destruction and degeneration. MS patients often have a relapsing-remitting disease (RR) course. This manifests as sporadic neurological symptoms such as ataxia, fatigue and sensory impairment. Although many effective treatments can treat inflammatory relapses in RRMS patients, most of them will eventually develop progressive disease. This is characterised by a gradual and irreversible accumulation of disabilities. The lack of biological targets that can be used to treat progressive MS (PMS), and the consequent dearth of effective drugs, makes it challenging to provide therapeutic intervention.
PMS medications are rare. They have limited efficacy in treating active forms of the disease. They also don’t slow down degeneration and do not promote repair. These unmet medical needs are why stem cell therapies have many compelling therapeutic benefits. Stem cell transplantation has the potential to provide neurotrophic support, immunomodulation, and cell replacement. It is also promising in combating chronic neuroinflammation. We will discuss the current state and future prospects for stem cell transplantation in PMS treatment.
Using Hematopoietic Stem Transplantation to Treat Multiple Sclerosis
Curative therapy is rare in the field of autoimmune disease. Drugs have many limitations, and side effects can occur. Patients and medical scientists are always interested in finding new treatments. A perfect example is Multiple sclerosis (MS), an autoimmune, chronic and inflammatory disease that can destroy the central nervous system (CNS), myelin, and varying degrees of damage to the axons, is an example. Myelin, a lipid coating that surrounds the Axon of nerve cell cells, electrically insulations sections of the Axon. It makes up a large portion of the brain’s ‘white matter.
Myelin is formed by Schwann cells. Its function is to accelerate nerve conduction throughout our nervous system. It is more common in young adults than in men and affects about half of all people. Researches published in the 1990s showed that animal models and theoretical considerations regarding hematopoietic cell transplantation (HSCT) were useful in preventing and treating autoimmune disorders. Clinical responses were seen in some patients suggesting that high-dose chemotherapy could be followed by HSCT rescue to “reset” immunological changes by controlling autoreactive clones. This would then be followed by immunological tolerance and immune reconstitution.
After the MS patient receives cyclophosphamide or filgrastim, the stem cells are taken from their bone marrow. The chemotherapy effects reduce the number of lymphocytes in the final stem-cell collection. Next, more chemotherapy is given, and the stem cells are instilled in the patient. Many studies have shown that HSCT is a viable treatment option for MS. More than 1000 HSCTs were performed worldwide. Patients have received treatment in either small trials or multicenter studies.
It has been shown that mesenchymal stem cells taken from bone marrow can transform into Schwann cells and regenerate myelin. The injection of mesenchymal stem cells into the spinal cord of demyelinated animals resulted in the recovery of mobility and myelin regeneration.
Similar results were reported in patients after injections of autologous stem cells in the spinal cord. It is sometimes difficult to pinpoint the degenerative areas. Sometimes, injecting stem cells into the bloodstream can provide even better results.
Endogenous Stem Cell Mobilisation
To prove that ESCM is clinically relevant, it must be shown that stem cells play a role in tissue repair following injury or other degenerative conditions. The clinical value of mobilising endogenous bone marrow-derived stem cells (BMSC) would be to increase the availability of stem cells that can migrate into the affected tissues and aid in tissue repair.
Granulocyte-Colony Stimulating factor (G-CSF) is the most commonly known compound that naturally stimulates BMSC mobilisation. G-CSF, a cytokine that is secreted by different tissues, was discovered in 1985. It stimulates the growth, differentiation, and function of both neutrophil precursors as well as mature neutrophils. G-CSF has been shown to stimulate BMSC mobilisation. This makes it a common tool for protocols of stem cell apheresis, which is used to preserve stem cells and transplant stem cells.
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G-CSF can cause severe side effects in people and should not be used as a treatment. Alternative options include plant extracts, which have been shown to trigger Endogenous Stem Cell Mobilisation. These plants are known as “Stem Cell Enhancers”. Stemregen is a combination of some of the most potent Stem Cell Enhancers known to date. Although their effects are milder, long-term usage can result in significant nerve repair, including MS benefits.
ESCM is beneficial in treating various degenerative conditions in animals and humans. In some cases, BMSC can migrate into tissues and contribute directly to forming new functional somatic cell types in the target tissue. In other cases, such as those involving the heart or central nervous system diseases, the primary mechanism of action is the secretion paracrine, which stimulate the proliferation and differentiation of tissue stem cells.
Many stem cell mobilisers have been studied in scientific literature. Many of these have side effects that make it difficult to apply in humans what has been proven effective in animal models. G-CSF, Stem Cell Factor and others have been linked to side effects ranging from nausea, vomiting, pain, numbness, pericarditis, and thrombosis. Despite the potential benefits, these side effects have largely stopped the use of such compounds in ESCM in humans. This is largely why there has been so little interest in this therapeutic approach. Safe stem cell mobilisers are the main obstacle to further investigation of ESCM’s therapeutic potential.
THE THERAPEUTIC POTENTIAL OF STIMULATING ENDOGENOUS STEM CELL MOBILISATION by Alan Lichtbroun
PMID: 29772133 DOI: 10.3727/036012917×14908026365016
Dezawa M, Takahashi I, Esaki M, et al. (2001) Sciatic nerve regeneration in rats induced by transplantation of in vitro differentiated bone-marrow stromal cells. Eur. J. Neurosci. 14, 1771-1776. https://pubmed.ncbi.nlm.nih.gov/11860471/
Akiyama Y, Radtke C, and Kocsis JD. (2002) Remyelination of the rat spinal cord by transplantation of identified bone marrow stromal cells. J Neurosci. 22(15):6623-30. https://pubmed.ncbi.nlm.nih.gov/12151541/
Cuevas P, Carceller F, Dujovny M, et al. (2002) Peripheral nerve regeneration by bone marrow stromal cells. Neural Res. 24: 634-638. https://pubmed.ncbi.nlm.nih.gov/12392196/
Saccardi R, Mancardi GL, Solari A, et al. (2005) Autologous HSCT for severe progressive multiple sclerosis in a multicenter trial: impact on disease activity and quality of life. Blood 105:2601-2607. https://pubmed.ncbi.nlm.nih.gov/15546956/
Inoue M, Honmou O, Oka S, et al. (2003) Comparative analysis of the remyelinating potential of focal and intravenous administration of autologous bone marrow cells into the rat demyelinated spinal cord. Glia. 44(2):111-8. https://pubmed.ncbi.nlm.nih.gov/14515327/