Multiple Sclerosis Society of Canada

Stem Cells

Stem cells are cells in the body that can mature into specialized cells that serve a specific function. They are also able to produce exact copies of themselves. There are two main types of stem cells: embryonic stem cells and adult stem cells.

  • Embryonic stem cells are found in the developing embryo and can mature into most types of cells in the body. The incredible flexibility of these stem cells highlights their usefulness for tissue healing and regeneration; however, there exists ethical debate over the use of stem cells from embryos.
  • Adult stem cells are found in some adult tissues and organs including the bone marrow, skin, blood, and brain. Adult stem cells are not as flexible as embryonic stem cells and are therefore more limited in terms of the types of cells they mature into.

The unique properties of stem cells provide promise for new treatments that can slow/halt MS disease activity and repair tissue damage in the central nervous system. In addition to ethical concerns surrounding the use of stem cells, legitimate health concerns exist as well. Stem cell treatments can be invasive and risky procedures, as these cells have the potential to develop into tumours.

Types of stem cells:

Hematopoietic Stem Cells

Hematopoietic stem cells (HSC) are found in bone marrow, blood, and umbilical cord. These stem cells are capable of maturing into all cells that comprise the blood and immune system. They have been used for many years to treat leukemia, lymphoma, and blood disorders. HSC transplant is a risky procedure with a reported 1-2% death rate. The procedure involves collecting stem cells from an individual’s own (autologous) bone marrow. The individual is then subjected to chemotherapy to deplete the immune system and stem cells are reintroduced into the body where they mature into new, healthy immune cells. Stem cells can be injected into the body in different ways. Generally, stem cells are administered intravenously (an injection into the vein) or intrathecally (an injection into the space around the spinal cord) and less commonly intraparaenchymally (an injection into the brain).

Autologous HSC transplants (or aHSCT) have been tested in people with highly active forms of MS who are unresponsive to other treatments and have a poor prognosis. The primary objective for this type of transplant is to reboot the immune system which is thought to be causing damage to nerve cells in MS. The goal of the procedure is to provide the person with a new, healthy immune system that will no longer attack myelin. In 2000, the MS Society of Canada and MS Scientific Research Foundation funded a clinical trial involving HSC transplants, led by Drs. Mark Freedman and Harry Atkins from the Ottawa Hospital Research Institute/University of Ottawa. For more information see Canadian Bone Marrow Transplantation (BMT) Trial.

The aHSC therapy available in Canada is a treatment that uses high-dose chemotherapy, also called conditioning. There are currently three sites in Canada, The Ottawa Hospital, Foothills Medical Centre in Calgary, and Le Centre hospitalier de l'Université de Montréal (CHUM), accepting referrals for individuals who are eligible for aHSCT. Speak to your neurologist if you are exploring this treatment option. Questions related to the procedure such as payment/coverage details, eligibility and monitoring should be directed to the clinic coordinator at each site.

Other aHSCT trials have been completed or are currently taking place around the world. These trials include different methods, eligibility criteria, and chemotherapy regimens and each treatment protocol will bring different risks and outcomes. Together this body of research, has greatly enhanced our understanding of the full risks and benefits associated with aHSCT as a treatment for MS, and paves the way for ongoing research on treatments involving stem cells for all forms of MS. The Canadian BMT trial offers a unique perspective on the sustained effect of this treatment over the long term, reducing the need for ongoing treatment by a DMT and some patients achieved a halt in their disability progression or a return of function. While these outcomes can not be predicted for each individual, studies such as the Canadian trial, have identified that benefits of aHSCT are more likely to be seen in younger individuals (under the age of 40) with aggressive early disease despite treatment and without concerning comorbidities. Research suggests that aHSCT procedures to date have not been efficacious in people who have experienced a high level of MS-related disability over a prolonged period and/or exhibit low levels of inflammation in the brain and spinal cord. 

Mesenchymal Stem Cells

Mesenchymal stem cells (MSC) are found in many places in the body including the bone marrow, skin, and fat. While MSCs showed promise to suppress inflammation and repair nerve tissue in animal models, results from an international phase II clinical trial, MEsenchymal StEm cells for Multiple Sclerosis (MESEMS) were unable to demonstrate that MSC treatment was effective at reducing inflammatory activity in individuals with active relapsing-remitting or progressive MS as defined by recent relapses and/or evidence of MRI activity. MESCAMS (MEsenchymal StEm cell therapy for CAnadian MS patients) is the Canadian arm of the international MESEMS clinical trial which was performed across fifteen sites and ten countries. Unlike the aHSCT procedure, the MSC trial did not include chemotherapy. For more information see MEsenchymal Stem cell therapy for CAnadian MS patients (MESCAMS).

Though these findings do not support autologous MSC for treatment of active relapsing-remitting, primary or secondary progressive MS, MSC have demonstrated neuroprotective and tissue repair properties in other studies involving animal models of MS. More evidence is needed to assess the efficacy of MSC treatment to understand whether they can repair tissue to reduce disease worsening and prevent disability progression.

Neural Stem Cells

Neural stem cells (NSC) are found in the brain and are able to mature into various types of brain cells including neurons, oligodendrocytes, and astrocytes. NSCs may protect the brain and modulate the immune system. Early clinical trials in non-human primates demonstrated that treatment with NSCs benefitted the progression of an MS-like disease and recently, two Phase 1 trials have been completed however the findings have not yet been published. Additional clinical trials in humans are required to determine the safety and efficacy of NSC therapy.

As demonstrated by the examples above, there is a vast array of research taking place which will provide additional answers about the use of stem cells to treat MS. Results published thus far are promising and will continue to build on the body of evidence making it possible to determine what kind of stem cells can be used, optimal delivery methods, and which forms of MS may benefit from the different stem cell procedures.

References

  1. Iajimi, A.A. et al. Feasibility of cell therapy in multiple sclerosis: A systematic review of 83 studies. IJHOSCR. 2013; 7.
  2. Holloman, J.P. et al. The development of hematopoietic and mesenchymal stem cell transplantation as an effective treatment for multiple sclerosis. Am J Stem Cell. 2013; 2: 95-107.
  3. Fassas A, et al. Long-term results of stem cell transplantation for MS: a single-center experience. Neurology. 2011; 76(12):1066-1070.
  4. Uccelli A, Laroni A, Ali R, Battaglia MA, Blinkenberg M, Brundin L, Clanet M, Fernandez O, Marriot J, Muraro P, Nabavi SM, Oliveri RS, Radue E, Ramo Tello C, Schiavetti I, Sellner J, Sorensen PS, Sormani MP, Wuerfel JT, Freedman MS; MESEMS investigators. Safety, tolerability, and activity of mesenchymal stem cells versus placebo in multiple sclerosis (MESEMS): a phase 2, randomised, double-blind crossover trial. Lancet Neurol. 2021 Nov;20(11):917-929. Erratum in: Lancet Neurol. 2022 Jan;21(1)
  5. Inoue M et al. Comparative analysis of remyelinating potential of focal and intravenous administration of autologous bone marrow cells into the rat demyelinated spinal cord. Glia. 2003; 44 (2):111–118.
  6. Akiyama Y et al. Remyelination of the spinal cord following intravenous delivery of bone marrow cells. Glia. 2002; 39(3):229–236.
  7. Harris VK etal. Characterization of autologous mesenchymal stem cell-derived neural progenitors as a fea¬sible source of stem cells for central nervous system applications in multiple sclerosis. Stem Cells Transl Med 2012; 1: 536-547.
  8. Giannakopoulou A et al. Inflammatory changes induced by transplant¬ed neural precursor cells in a multiple sclero¬sis model. Neuroreport. 2011; 22: 68-72
  9. Harris VK et al. Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural progenitors in an experi¬mental model of multiple sclerosis. J Neurol Sci 2012; 313: 167-177.
  10. Ben-Hur T. Immunomodulation by neural stem cells. J Neurol Sci. 2008; 265(1-2):102-4.
  11. Pluchino S, et al. Human neural stem cells ameliorate autoimmune encephalomyelitis in non-human primates. Ann Neurol. 2009; 66(3):343-54.
  12. Darling PJ et al. Diminished Th17 (Not Th1) Responses Underlie Multiple Sclerosis Disease Abrogation after Hematopoietic Stem Cell Transplantation. Annals of Neurology, 2012 Oct 11.
  13. Bai L et al. Hepatocyte growth factor mediates MSCs stimulated functional recovery in animal models of MS. Nature Neuroscience. 2012; 15(6): 862-870.
  14. Smith JA, Nicaise AM, Ionescu RB, Hamel R, Peruzzotti-Jametti L, Pluchino S. Stem Cell Therapies for Progressive Multiple Sclerosis. Front Cell Dev Biol. 2021;9:696434. Published 2021 Jul 9.
  15. Bose, G., Thebault, S., Atkins, H., & Freedman, M. (2020). Does Resetting the Immune System Fix Multiple Sclerosis? Canadian Journal of Neurological Sciences / Journal Canadien Des Sciences Neurologiques, 47(1), 1-10. doi:10.1017/cjn.2019.294

Additional Information

MSIF: Stem Cells and Regeneration

Canadian Stem Cell Foundation

Stem Cell therapies in MS Publication

National MS Society (NMSS) Momentum: New hope for repairing myelin damage in MS

MS Trust: Can stem cell transplants treat MS?

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