HSCT for Multiple Sclerosis in 2023
This article will explain what Haematopoietic stem cell transplantation (HSCT) involves, its benefits/risks, and how it may or may not be helpful for certain neurological conditions.
![HSCT for Multiple Sclerosis in 2023](jpg/61fc1caf12cbacd6edd1c602_hsct2.jpg)
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What is HSCT?
Hematopoietic stem cell transplantation (HSCT) is a treatment approach that aims to eliminate disease activity by first eradicating the immune system using cytotoxic drugs (chemotherapy) followed by the introduction of autologous hematopoietic (blood-derived) stem cells to aid in re-building the lost immune system. (1)
Bone Marrow Transplantation (HSCT) can be broken down into four separate parts:
1) Mobilization: drugs are administered to help mobilize hematopoietic stem cells from bone marrow (stimulate stem cell production within bone marrow stem cells & promote release into the blood) (5)
2) Harvest: the cells are obtained/extracted from the patients bone marrow (autologous cell extraction)
3) Conditioning: cytotoxic drugs (chemotherapy) or radiation are used to "destroy" or "reset" the immune system
4) Infusion: administration of autologous Hematopoietic stem cells (HSCs) derived from bone marrow to help speed up recovery. The immune system can take up to 3-6 months to rebuild itself.
Eliminate the immune system
A recently published study by Burman et al. states that the basis of HSCT operates on the belief that the origin of neurological conditions lie exclusively in the immune system and is dependant on immunological memory. (1) Thus if the immune system is destroyed, it will be reset and therefore will not malfunction as it did previously.
According to Burman et al. one misconception is that the Haematopoietic stem cells (HSCs) are the therapeutic product which they are not.
"HSCs do not differentiate into neurons, and there is no evidence that they can repair damaged central nervous system (CNS) tissue."
The term "autologous hematopoietic stem cell transplantation" can be misleading since the autologous stem cells are a supportive blood product that helps to speed up recovery after intense immunosuppressive therapy. (1)
Therefore Haematopoietic stem cell transplantation (HSCT) should generally be considered a form of high dose immunosuppressive therapy with hematopoietic stem cell support. Rather than an alternative type of stem cell therapy.
What are hematopoietic stem cells?
Also known as stem cells obtained from blood. A hematopoietic stem cell is a type of stem cell that can develop into all types of blood cells, including red blood cells, white blood cells, and platelets. (3) Hematopoietic stem cells can be found in the peripheral blood and bone marrow, the stem cells must first be mobilized via certain drug administration before extraction from the patient.
What is hematopoietic stem cell transplantation (HSCT) used for?
Hematopoietic stem cell transplantation (HSCT) can be used for a variety of neurological or neuroinflammatory conditions such as Multiple Sclerosis (MS), Neuromyelitis Optica, Chronic Inflammatory Demyelinating PolyNeuropathy, and Myasthenia Gravis. HSCT has also shown the ability to help patients with Sickle Cell Disease (SCD), a genetically inherited red blood cell disorder.
What are the side effects of HSCT?
According to Burman et al., there can be a variety of adverse reactions from Hematopoietic stem cell transplantation (HSCT). These are divided into long-term side effects and acute toxicity (describes adverse effects of a substance in a short amount of time). (1)
Short term side effects
Some of the short term side effects of HSCT are alopecia (loss of hair), anemia, leucopenia (lowered white blood cell count - a decrease in disease-fighting cells in your body), and fever with or without a blood bacterial infection. Antibiotics are commonly needed to help combat bacterial infections that may occur after cytotoxic drug intake.
These short term side effects or acute toxicity is directly related to the intensity and invasiveness of the cytotoxic immunosuppressive treatment and damaged immune system.
Long term side effects
Long term side effects have been much less studied. Burman describes this as a major gap in the knowledge base of Hematopoietic stem cell transplantation (HSCT) as a treatment. "The main concerns are viral reactivations, development of secondary autoimmunity, malignancies and impaired fertility." (1)
Chemotherapy can also cause a variety of other long term health problems including: heart issues including Congestive heart failure (CHF), Arrhythmia, and Coronary artery disease; lung issues, endocrine system problems, hormonal problems, bone joint and soft tissue problems such as osteoperosis, digestive issues and brain / spinal cord problems. (9)
HSCT for Multiple Sclerosis (MS)
Hematopoietic stem cell transplantation (HSCT) for MS can be classified as a high dose immunosuppressant therapy with hematopoietic stem cell support that aims to halt disease activity by destroying then rebuilding the immune system.
A large number of uncontrolled studies have been published throughout the years which have established that HSCT can have an effect on inflammation in MS and it can prevent relapses and new MRI lesions. (1)
According to the National MS Society, only certain people with MS may be candidates for Hematopoietic stem cell transplantation (HSCT). The best candidates for this procedure are people under the age of 50, have had MS for 10 years or less, or have relapsing MS and have had “breakthrough” disease activity (new inflammatory MS lesions in the central nervous system, and/or clinical relapses) despite treatment with a highly effective disease-modifying therapy (or for whom the use of a highly effective disease-modifying therapy is contraindicated) (6)
Cord Blood and HSCs
Cord blood is the blood that remains in the umbilical cord and placenta after a baby is born. It is a rich source of haematopoietic stem cells (HSCs), which are a type of stem cell that gives rise to all of the different blood cells in the body, including white blood cells, red blood cells, and platelets.
Haematopoietic stem cell transplantation (HSCT) is a medical procedure in which HSCs are transplanted from one individual to another in order to treat a variety of conditions, such as blood disorders, immune system disorders, and certain types of cancer. Cord blood can be used as a source of HSCs for HSCT, and it has several advantages over other sources of stem cells.
One advantage of using cord blood for HSCT is that it is less likely to cause graft-versus-host disease (GVHD) than other sources of stem cells, such as bone marrow or peripheral blood. This is because cord blood stem cells are less mature and have not yet been exposed to the same range of antigens as stem cells from other sources, making them less likely to attack the recipient's body. Cord blood stem cells are also easier to match with the recipient, which further reduces the risk of GVHD.
In addition to these advantages, cord blood is also a readily available source of stem cells, as it can be collected immediately after birth and stored until it is needed for transplantation. However, one disadvantage of using cord blood for HSCT is that it contains a smaller number of stem cells than other sources, so it may not be suitable for adults or for certain types of transplants.
Is HSCT FDA Approved?
Only the individual medications and procedures that encompass Hematopoietic stem cell transplantation (HSCT) have been approved by the FDA. These include cytotoxic drugs, radiation, chemotherapy, antibiotics, etc. However, HSCT as a treatment for specific conditions has not yet been approved by the FDA. Currently, to participate in a bone marrow transplantation within the United States, MS patients must enroll in an active clinical trial.
How does HSCT differ from mesenchymal stem cell therapy (MSCT)?
Many peer-reviewed studies over the years have found that mesenchymal stem cell therapy (MSCT) has strong anti-inflammatory and immunosuppressive properties. The intravenous administration of mesenchymal stem cells (MSCs) can improve the healing of neural, renal, and lung injuries in many different models. (7) Mesenchymal stem cell therapy (MSCT) also can induce large periods of remission and may help improve MS symptoms including; loss of strength, mobility, flexibility, numbness, and overall mobility.
The two treatment options (HSCT & MSCT) aim to achieve the same outcome: prevent relapses, new MRI lesions, and improve disability.
Mesenchymal stem cell therapy (MSCT) aims to prevent relapses, new MRI lesions, and improve disability without the need for invasive cytotoxic immunosuppression therapy (Chemotherapy). MSCT can reduce inflammation and regulate the immune system, both of which play a strong role in helping improve MS symptoms and promote disease remission.
According to a recent study published by Regmi and colleagues:
"The immunosuppressive activities of MSCs are initiated by cell-to-cell contact and the release of immunoregulatory molecules. By doing so, MSCs can inhibit the proliferation and function of T cells, natural killer cells, B cells, and dendritic cells, and can also increase the proliferation of regulatory T cells." (8)
Choose the treatment that is right for you
Results for Hematopoietic Stem Cell Transplants (HSCT) have been mostly positive for autoimmune diseases, such as Multiple Sclerosis, in which the immune system attacks a patient’s body. The treatment “resets” the immune system, hoping to cease the effects of the disorder. However, many patients may be turned off by the use of chemotherapy and the inherent risks associated with such aggressive treatment. Some patients may be in too poor a condition to even attempt this form of treatment. Although safety has dramatically improved with experience, HSCT initially had a 1 in 100 death rate for participants.
Mesenchymal stem cell therapy (MSCT) is a much less invasive and radical procedure, having little impact on the patient. Mesenchymal stem cell therapy (MSCT) gives patients an option for effective treatment without the risk of chemotherapy, or who may be in too poor a condition to undergo Hematopoietic Stem Cell Transplants HSCT. Additionally, the non-invasive nature of Mesenchymal Stem Cell Therapy (MSCT) allows for repeat treatment over time without continuous damage being done to the body.
Mesenchymal stem cell therapy (MSCT) and HSCT are very different procedures. Hematopoietic stem cell transplantation (HSCT) should generally be considered a form of high dose immunosuppressive therapy with hematopoietic stem cell support. Rather than an alternative type of stem cell therapy. Mesenchymal stem cell therapy has shown similar outcomes to HSCT without the need for aggressive cytotoxic drugs (Chemotherapy). It is also important to note that cord tissue-derived mesenchymal stem cell therapy has shown the ability to avoid a negative response from a person’s immune system, allowing the cells to be transplanted in a wide range of people without fear of rejection. These transplants vastly increase the body’s natural healing abilities and have potent anti-inflammatory and immunosuppressive responses.
Graft Versus Host Disease and Bone Marrow Transplant
Graft Versus Host Disease can occur when the HSCs from the donor (the "graft") recognize the recipient's body (the "host") as foreign and launch an immune response against it. This can lead to the destruction of healthy cells in the host's body, leading to a range of symptoms, including skin rash, diarrhea, liver damage, and difficulty breathing. Graft Versus Host Disease (GVHD) can be severe or even life-threatening in some cases.
To reduce the risk of Graft Versus Host Disease (GVHD), doctors will often try to match the donor and recipient as closely as possible in terms of their human leukocyte antigens (HLAs), which are proteins found on the surface of cells that help the immune system distinguish between self and non-self. However, even when the donor and recipient are well-matched, there is still a risk of GVHD occurring.
So does the immune system need to be destroyed to effectively help neurological conditions such as MS?
No, it does not. Published studies have found that Mesenchymal stem cell therapy (MSCT) can reduce inflammation and regulate the immune system, without the need for invasive immunosuppressive treatments (chemotherapy). MSCs derived from umbilical cord tissue also offer intrinsic benefits that hematopoietic stem cells do not, such as the ability to differentiate into a variety of cell types, release of immunoregulatory molecules, promote the release of exosome and growth factors.
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Glossary:
Hematopoietic: relating to, or involved in the formation of blood cells
Autologous: derived from the same individual, or involving one individual ad both donor and recipient
Allogeneic: involving, derived from, or being individuals of the same species that are sufficiently unlike genetically to interact antigenically
References:
(1) Burman, J., Tolf, A., Hägglund, H., & Askmark, H. (2018, February). Autologous haematopoietic stem cell transplantation for neurological diseases. Retrieved December 09, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800332/
(2) Hematopoietic Medical Definition. (n.d.). Retrieved December 09, 2020, from https://www.merriam-webster.com/medical/hematopoietic
(3) NCI Dictionary of Cancer Terms. (n.d.). Retrieved December 10, 2020, from https://www.cancer.gov/publications/dictionaries/cancer-terms/def/hematopoietic-stem-cell
(4) Bhatia, M., & Sheth, S. (2015, July 10). Hematopoietic stem cell transplantation in sickle cell disease: Patien: JBM. Retrieved December 10, 2020, from https://www.dovepress.com/hematopoietic-stem-cell-transplantation-in-sickle-cell-disease-patient-peer-reviewed-article-JBM
(5) Bone Marrow Stem Cell Transplant – HSCT. (2020, December 04). Retrieved December 11, 2020, from https://www.nationalmssociety.org/Research/Research-News-Progress/Stem-Cells-in-MS/Bone-Marrow-Stem-Cell-Transplant-%E2%80%93-HSCT
(6) National MS Society Releases Recommendations for HSCT-Bone Marrow Transplant for MS. (2020, November 11). Retrieved December 11, 2020, from https://www.nationalmssociety.org/About-the-Society/News/National-MS-Society-Releases-Recommendations-for-a
(7) Sundin, M., Barrett, A., Ringdén, O., Uzunel, M., Lönnies, H., Dackland, A., . . . Blanc, K. (2009, September). HSCT recipients have specific tolerance to MSC but not to the MSC donor. Retrieved December 11, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747778/
(8) Shobha Regmi, Shiva Pathak, Jong Oh Kim, Chul Soon Yong, Jee-Heon Jeong, Mesenchymal stem cell therapy for the treatment of inflammatory diseases: Challenges, opportunities, and future perspectives, European Journal of Cell Biology, Volume 98, Issues 5–8, 2019, 151041, ISSN 0171-9335, https://doi.org/10.1016/j.ejcb.2019.04.002. (http://www.sciencedirect.com/science/article/pii/S0171933519300378)
(9) Long-Term Side Effects of Cancer Treatment. (2020, December 10). Retrieved December 11, 2020, from https://www.cancer.net/survivorship/long-term-side-effects-cancer-treatment