Multiple sclerosis is a systemic autoimmune disease. It affects the central nervous system, which encompasses both the brain and the spinal cord.
In patients with MS, the immune system attacks the myelin sheath that protects nerve endings and connections. These inflammatory lesions are often visible through MRI scans. They progressively impair communication between nerves and motor cells. This disease is particularly feared because it leads to the progressive loss of limb function and movement.
Symptoms of Multiple Sclerosis
The exact symptoms experienced by a patient with multiple sclerosis will vary depending on the areas attacked by the autoimmune inflammatory process. However, as demyelinating lesions accumulate, so do the flare-ups of the disease and the intensity of the symptoms.
Eventually, patients will develop secondary of intractable disease.
Standard Treatment for Multiple Sclerosis
Multiple sclerosis (MS) is mainly treated with a combination of conventional oral medication or injectable drugs.
Some patients with relapsing remitting MS may respond to the treatments available for MS and manage to minimize the frequency of recurrent attacks or prevent them altogether. Unfortunately, patients with the non-responding disease, and the overwhelming majority of patients with primary or secondary progressive MS, do not respond to conventional medications available for MS. Such patients are regarded as incurable.
The use of non-invasive and safe deep transmagnetic stimulation (dTMS) available at Biotherapy International, is a new approach already approved for the treatment of several neuroinflammatory and neurodegenerative disorders including MS.
Use of Mesenchymal Stem Cells for the treatment of Multiple Sclerosis
Patients with uncontrolled or progressive disease may benefit from immunosuppressive medications, sometimes even following more aggressive conditioning designed to ablate all mature lymphocytes, including self-reactive T cells, alongside autologous hematopoietic stem cell transplantation (HSCTs). Following HSCT, newly generated T cells may be trained to acquire self-tolerance. This will reconstitute a patient’s normal immune system, allowing it to terminate otherwise resistant disease.
This process is similar to the induction of self-tolerance in utero during embryogenesis at the early stages of pregnancy. Unfortunately, HSCT is a major procedure with serious potential risks.
Thanks to its capacity to induce anti-inflammatory and immune regulatory effects, treatment with autologous MSCs, or even from those coming from an unrelated placenta and cord tissue, represent a safe alternative treatment for patients with MS. In theory, since MSCs are truly multi-potent, a patient’s own MSCs may potentially be differentiated to oligodendrocytes (or myelin-synthesizing cells) and then used to induce re-myelination.
Alternatively, nanoparticles secreted by MSCs may induce remyelination by differentiating a locally residing patient’s own MSCs. Supported by our pre-clinical investigations and based on our clinical experience, a large number of patients with MS who fail to respond to conventional MS medications may benefit from safe outpatient treatment with MSCs. Unfortunately, at present, the use of MSCs enriched ex vivo in cell-processing centres is not approved by regulatory authorities.
Because of these regulatory barriers, MSC-based treatments for MS or for other resistant autoimmune diseases can only be accomplished in one of our satellites clinics abroad, in places with more permissive regulations.
As an alternative, a combination of different treatments can be used with similar expected effects. This involved using immunosuppressive treatments to minimize the proportions of self-reactive lymphocytes, followed by the use of growth factors to stimulate the secretion of multipotent stem cells from the bone marrow. These can then be enriched alongside newly-derived normal T cells. This treatment can be regarded as a safe micro-HSCT, and can replace the combination of more hazardous HSCT with dTMS.
Furthermore, circulating MSCs may be targeted to the central nervous system by safe and non-invasive low energy acoustic shockwave therapy (AST), which dilates the blood vessels and increases the flow of regulatory cells to the central nervous system. Exposure of circulating multipotent stem cells to harmless low energy multi-colour laser light therapy (LLLT) can also be used to activate and enhance the regenerative capacity of multipotent MSCs.The supportive use of all three devices– dTMS, AST and LLLT – can be applied to improve the outcome of cell therapy for MS patients. It can also be used for other indications in need of regenerative medicine, among both patients treated by MSCs expanded ex vivo and those treated by enrichment of autologous multi-potent stem cells.
Our Scientific Researches and Patents on the use of Stem Cells for Treatment
- Karussis D, Grigoriadis S, Polyzoidou E, Grigoriadis N, Slavin S, Abramsky O. Neuroprotection in multiple sclerosis. Clin Neurol Neurosurg. 2006 Mar;108(3):250-4.
- Burt RK, Cohen B, Rose J, Petersen F, Oyama Y, Stefoski D, Katsamakis G, Carrier E, Kozak T, Muraro PA, Martin R, Hintzen R, Slavin S, Karussis D, Haggiag S, Voltarelli JC, Ellison GW, Jovanovic B, Popat U, McGuirk J, Statkute L, Verda L, Haas J, Arnold R. Hematopoietic stem cell transplantation for multiple sclerosis. Arch Neurol. 2005 Jun;62(6):860-4. Review.
- Prigozhina TB, Khitrin S, Elkin G, Eizik O, Morecki S, Slavin S. Mesenchymal stromal cells lose their immunosuppressive potential after allotransplantation. Exp Hematol. 2008 Oct;36(10):1370-6.
- Slavin S, Kurkalli BG, Karussis D. The potential use of adult stem cells for the treatment of multiple sclerosis and other neurodegenerative disorders. Clin Neurol Neurosurg. 2008 Nov;110(9):943-6.
- Karussis D, Kassis I, Kurkalli BG, Slavin S. Immunomodulation and neuroprotection with mesenchymal bone marrow stem cells (MSCs): a proposed treatment for multiple sclerosis and other neuroimmunological/neurodegenerative diseases. J Neurol Sci. 2008 Feb 15;265(1-2):131-5.
- Kassis I, Grigoriadis N, Gowda-Kurkalli B, Mizrachi-Kol R, Ben-Hur R, Slavin S, Abramsky O, Karussis D. Neuroprotection and immunomodulation with mesenchymal stem cells in chronic experimental autoimmune encephalomyelitis. Arch Neurol. 2008;65(6):753-761.
- Gurevitch O, Slavin S, Resnick I, Khitrin S, Feldman A. Mesenchymal progenitor cells in red and yellow bone marrow. Folia Biol (Praha). 2009;55(1):27-34.
- Karussis D, Karageorgiou C, Vaknin-Dembinsky A, Gowda-Kurkalli B, Gomori JM, Kassis I, Bulte JW, Petrou P, Ben-Hur T, Abramsky O, Slavin S. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol. 2010 Oct;67(10):1187-94.
- Freedman MS, Bar-Or A, Atkins HL, Karussis D, Frassoni F, Lazarus H, Scolding N, Slavin S, Le Blanc K, Uccelli A. The therapeutic potential of mesenchymal stem cell transplantation as a treatment for multiple sclerosis: consensus report of the International MSCT Study Group. Mult Scler. 2010 Apr;16(4):503-10.
- Tichon A, Eitan E, Kurkalli BG, Braiman A, Gazit A, Slavin S, Beith-Yannai E, Priel E. Oxidative stress protection by novel telomerase activators in mesenchymal stem cells derived from healthy and diseased individuals. Curr Mol Med. 2013 Jul;13(6):1010-22.
- Kazimirsky G, Jiang W, Slavin S, Ziv-Av A, Brodie C. Mesenchymal stem cells enhance the oncolytic effect of Newcastle disease virus in glioma cells and glioma stem cells via the secretion of TRAIL. Stem Cell Res Ther. 2016 Oct 10;7(1):149.
- Ohtake T, Kobayashi S, Slavin S, Mochida Y, Ishioka K, Moriya H, Hidaka S, Matsuura R, Sumida M, Katagiri D, Noiri E, Okada K, Mizuno H, Tanaka R. Human Peripheral Blood Mononuclear Cells Incubated in Vasculogenic Conditioning Medium Dramatically Improve Ischemia/Reperfusion Acute Kidney Injury in Mice. Cell Transplantation 2018, Vol. 27(3) 520–530.
- Zilberman-Itskovich S, Abu-Hamad R, Zarura R, Sova M, Hachmo Y, Stark M, Neuman S, Slavin S, Efrati S. Human mesenchymal stromal cells ameliorate complement induced inflammatory cascade and improve renal functions in a rat model of ischemia-reperfusion induced acute kidney injury. PLoS One. 2019 Sep 12;14(9):e0222354. doi: 10.1371/journal.pone.0222354. eCollection 2019.
- Slavin S. Successful treatment of autoimmune disease in (NZB/NZW)F1 female mice by using fractionated total lymphoid irradiation. Proc Natl Acad Sci USA 1979;76:5274-5276.
- Fuks Z, Slavin S. The use of total lymphoid irradiation (TLI) as immunosuppressive therapy for organ allotransplantation and autoimmune diseases. Int J Rad Oncol Biol Phys 1981;7:79-82.
- Moscovitch M, Slavin S. Regulation of the immune response in experimental models of autoimmune disorders. 1. Immunocompetence and transplantation tolerance in (NZB x NZW)F1 hybrid mice immunosuppressed with total lymphoid irradiation and in reconstituted bone marrow chimeras. J Clin Lab Immunol 1983;4:185-191.
- Moscovitch M, Slavin S. Regulation of the immune response in experimental models of autoimmune disorders. 2. Induction of suppressor cells of the mixed lymphocyte culture in adult (NZB x NZW)F1 mice using total lymphoid irradiation. J Clin Lab Immunol 1983;11:67-74.
- Moscovitch M, Rosenmann E, Neeman Z, Slavin S. Successful treatment of autoimmune manifestations in MRL/1 and MRL/n mice using total lymphoid irradiation (TLI). Exp Molec Pathol 1983;38:33-47.
- Rossini AA, Slavin S, Woda BA, Geisberg M, Like AA, Mordes JP. Total lymphoid irradiation prevents diabetes mellitus in the bio-breeding/Worcester (BB/W) rat. Diabetes 1984;33:543-547.
- Slavin S. The use of total lymphoid irradiation (TLI) for the treatment of autoimmune disorders. Is J Med Sci 1988; 24:375-8.
- Karussis DM, Slavin S, Ben-Nun A, Ovadia H, Vourka-Karussis U, Lehmann D, Mizrachi-Kol R, Abramsky O. Chronic-relapsing experimental autoimmune encephalomyelitis (CR-EAE): treatment and indution of tolerance, with high dose cyclophosphamide followed by syngeneic bone marrow transplantation. J Neuroimmunol 1992;39:201-210.
- Karussis DM, Slavin S, Lehmann D, Mizrachi-Koll R, Abramsky O, Ben-Nun A. Prevention of experimental autoimmune encephalomyelitis and induction of tolerance with acute immunosuppression followed by syngeneic bone marrow transplantation. J Immunol 1992;148:1693-1698.
- Slavin S. Treatment of life threatening autoimmune diseases with myeloablative doses of immunosuppressive agents and autologous bone marrow transplantation – rationale and experimental background. BMT 1993;12:85-88.
- Slavin S, Karussis D, Weiss L, Vourka-Karussis U, Abramsky O. Immunohematopoietic reconstitution by allogeneic and autologous bone marrow grafts as a means for induction of specific unresponsiveness to donor-specific allografts and modified self in autoimmune disorders. Transplant Proc 1993;25:1274-1275.
- Karussis DM, Vourka-Karussis U, Lehmann D, Abramsky O, Ben-Nun A, Slavin S. Successful treatment of autoimmunity in MRL/lpr mice with T-cell depleted syngeneic bone marrow transplantation. EOS J Immunol Immunopharm 1993:XIII:78-79.
- Karussis DM, Lehmann D, Slavin S, Vourka-Karussis U, Mizrachi-Koll R, Ovadia H, Ben-Nun A, Kalland T, Abramsky O. Inhibition of acute, experimental autoimmune encephalomyelitis by the synthetic immunomodulator Linomide, Ann. Neurol 1993 34:(5);654-660.
- Slavin S, Karussis DM, Weiss L, Karussis-Vourka U and Abramsky O. Induction of tolerance to allo and self-antigens with syngeneic bone marrow transplantation. Transpl. Proc. 1993;25:1274-1275.
- Karussis DM, Vourka-Karussis U, Lehmann D, Abramsky O, Ben-Nun A, Slavin S. Immunomodulation of autoimmunity in MRL/1pr mice with syngeneic bone marrow transplantation (SBMT). Clin Exp Immunol1995;100(1):111-117.
- Blank M, Tomer Y, Slavin S, Shoenfeld Y. Induction of tolerance to experimental anti-Phospholipid syndrome (APS) by syngeneic bone marrow cell transplantation. Scand. J. Immunol 1995;42:226-234.
- Slavin S. Autologous and allogeneic stem cell transplantation for the treatment of autoimmune diseases as a potential new approach. The Decade of Autoimmunity. (Yehuda Shoenfeld, Editor) Elsevier. 1999:399-408.
- Slavin S, Nagler A. Bone marrow transplantation for cancer and autoimmunity. Cancer and Autoimmunity. Editors, Y. Shoenfeld and Eric Gershwin. Elsevier, 2000:409-421.
- Slavin S, Nagler A, Varadi G, Or R. Graft vs autoimmunity following allogeneic non-myeloablative blood stem cell transplantation in a patient with chronic myelogenous leukemia and severe systemic psoriasis and psoriatic polyarthritis. Exp Hematol 2000 Jul;28(7):853-7.
- Richard K. Burt, Walter Barr, Yu Oyama, Ann Traynor, Shimon Slavin. Future strategies in hematopoietic stem cell transplantation for rheumatoid arthritis. J of Rheumatology. 2001;28(64);42-48.
- Burt R.K, Slavin S, Burns W.H, Marmont A.M. Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: Getting closer to a cure? Blood, 2001;99(3)768-784.
- Slavin S, Paveletic S, Burt B. Allogeneic hematopoietic stem cell transplantation of rheumatoid arthritis. 2002.
- Burt R.K, Slavin S, Burns W.H, Marmont A.M. Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: Getting closer to a cure? Int J of Hematology 2002;76 (Suppl 1):226-247. Also presented at the 29th World Congress of the International Society of Hematology (2002 Seoul ISH). Seoul, Korea. August 24th-28th, 2002.
- Burt KR, Verda L, Oyama Y, Statkute L, Slavin S. Non-myeloablative stem cell transplantation for autoimmune diseases. Springer Semin Immun (2004) 26:57–69.
- Slavin S, Marmont A, Burt R. Allogeneic hematopoietic stem cell transplantation for autoimmune disease. Stem Cell therapy for Autoimmune Disease. Editors: Richard K. Burt & Alberto M. Marmont. Publishers: Landes Bioscience, Texas, USA. 2004:474-478.
- Burt RK, Verda L, Oyama Y, Statkute L, Slavin S. Non-myeloablative stem cell transplantation for autoimmune diseases. Chapter in Seminars and Immunopathology. Publisher Springer, Heidelberg, Germany. 2004;26:57-69.
- Burt R, Cohen B, Rose J, Petersen F, Oyama Y, Stefoski D, Katsamakis G, Carrier E, Kozak T, Muraro PA, Martin R, Hintzen R, Slavin S, Karussis D, Haggiag S, Voltarelli JC, Ellison GW, Jovanovic B, Popap U, McGuirk J, Statkute L, Verda L, Haas J, Arnold R. Hematopoietic stem cell transplantation for multiple sclerosis. Arch Neurol. 2005;62(6):860-864.