Regenerative Medicine and Stem Cells
Regenerative medicine is a new branch of medicine that specialises in restoring body tissues that were injured by disease, trauma or the aging process. It uses mesenchymal stromal stem cells (MSC), either derived from the patient, from a donor or related or unrelated placenta & cord tissue of a newborn baby.
It was previously documented that MSCs can be differentiated into bone-forming osteoblasts, cartilage-forming chondrocytes, or adipocytes that produce fat cells. However, recent scientific research shows that MSCs can transform into cells resembling many other tissues. This happens because the nucleus of these cells contains complete genetic information, which can be used to regenerate or repair damaged tissues and maintain a patient’s vital functions. In newborns, these stem cells can be found in either the placenta or the umbilical cord tissue. In adults, tMSCs can be extracted from the bone marrow or adipose tissue but much smaller concentrations are probably present in other tissues too.
In patients with conditions of the nervous system, MSCs migrate to the foci of inflammation to promote remyelination — the process that repairs the outer sheath that surrounds nerve fibres. Thanks to their anti-inflammatory effect, they also restore the structure of neurons and regulate autoimmune processes.
Due to their properties, MSCs are frequently used by orthopaedic surgeons and traumatologists. They have been successfully used to restore cartilage in damaged joints and ligaments, to promote the healing of complex bone fractures, and even to “grow” new bone using templates produced by 3D printers.
Thanks to their multi-system regenerative capacity, the use of multipotent MSCs can potentially be used as anti-aging treatment caused by normal age-related wear and tear and as such, slowing the ageing process, improve quality of life of elderly individuals, possibly even extending life expectancy, as suggested by animal experiments.
Which Diseases Can Respond to Treatment with MSCs?
In addition to their regenerative capacity, MSCs can induce potent anti-inflammatory effects and can also induce anti-fibrotic effects against scars of the skin and fibrosis of essential organs (e.g., liver cirrhosis). As such, treatment with MSCs has a wide range of indications, including for treatment of inflammatory and degenerative conditions, autoimmune diseases, and other conditions associated with pathologic fibrosis, which results from inflammation.
Due to their regenerative capacity, stem cell therapy can partially repair neurological damage caused by neuroinflammatory or neurodegenerative diseases such as multiple sclerosis, possibly also to a lesser extent amyotrophic lateral sclerosis, dementia, autism and Parkinson’s disease. The use of MSCs can help restore some functions of the nervous system after stroke and spinal cord injury as documented in pre-clinical animal experiments and pilot clinical trials.
At Biotherapy International, we used mesenchymal stem cells to treat diseases of the central nervous system, autism and spinal cord injury. Based on preclinical animal experiments and pilot clinical experience stem cell therapy may also prove effective for the treatment of renal failure, suggesting that the use of MSCs and in the future also their secretory nanoparticles know as exosomes or extracellular vesicles may be also used for the treatment of additional therapeutic indications.
How Safe is Stem Cell Therapy with MSCs?
Both MSCs and the active nanoparticles known as exosomes or extracellular vesicles they secrete can be safely injected intravenously, intrathecally and even directly to the subarachnoid space. Several hundred patients have received stem cell treatment at Biotherapy International and none have experienced severe side effects, while the majority achieved good treatment results and improved quality of life. It is important to note that Biotherapy International never uses embryonic stem cells, as repeated laboratory tests have shown that these can transform into malignant cells that provoke cancer. Unlike their embryonic counterparts, post-natal MSCs are completely safe for medicinal use. Due to recent regulations, treatment with MSCs processed by cultures in clean rooms can no longer be administered in Israel and treatment can be provided in one of Biotherapy International’s satellites. Alternatively, treatment with multipotent stem cells mobilized from the bone marrow into the circulation can be administered at Biotherapy International and such multipotent cells can be activated and targeted to their destination by non-invasive painless devices.
What is the Potential Advantage of Treatment with Mobilized Stem Cells at Biotherapy International in Tel Aviv?
In addition to treatment using MSCs in satellite centres abroad due to restrictive regulations by the Ministry of Health in Israel, at Biotherapy International we can provide treatment with patient’s multipotent stem cells by mobilizing such cells with agents that can mobilize stem cells from the bone marrow compartment into the blood. Circulating multi-potent stem cells can be activated and targeted to damaged organs by special non-invasive devices. Biotherapy International is the only clinic that uses 3 special devices to improve the therapeutic efficacy of circulating stem cells by combining activation, targeting and host-conditioning with deep trans-magnetic stimulation:
- Activation of circulating stem cells is attempted by exposing circulating cells using 4-color low-energy laser light therapy (blue, green, yellow and red laser light).
- Apply low energy acoustic waves topically, through an apparatus that expands the afferent blood vessels to increase the flow of stem cells into any targeted tissue. Such treatment can potentially increase the synthesis of biologically active substances that can activate mesenchymal stem cells.
- Specially designed deep trans-magnetic stimulation device (dTMS) is used to activate the targeted tissue, especially the central or peripheral nervous system. Interestingly, the use of dTMS for treatment of a long list of neuroinflammatory and neurodegenerative disorders was already approved in the US, Europe and Israel independently of administration of stem cells so we hope combining the use of stem cells and dTMS may provide synergistic therapeutic effects.
Peculiarities of Legislation in Therapy with Stem Cells
The use of multipotent stem cells for regenerative medicine is still new, so it has not yet passed legislative regulation in the USA, Europe or certain Asian countries. The concerns for MSC treatments by the public stems partly from its confusion with embryonic stem cells that are associated with the risk of developing malignant cells and for some carries both ethical and religious controversies. However, it has been proven that the use of adult mesenchymal stem cells, such as the ones recommended by Biotherapy International, does not carry any risk of transforming into malignant tissue while retaining a high therapeutic potential. The reservation of regulatory authorities is due to the lack of sufficiently large supportive prospective randomized trials. Lack of reliable information and confusion between embryonic and adult stem cells led to negative press reports, which harmed faster development of regenerative medicine.
Clinical trials involving MSCs are remarkably complex because, unlike drugs, each patient receives a personalized therapy regimen which unlike drugs is never the same. Besides, pharmaceutical companies that are willing to test new drugs are not interested in funding mesenchymal stem cell trials, since drugs are not needed for such therapy.
Nowadays, the FDA, several European countries, and the Israeli Ministry of Health are finally considering stem cells for official use. However, it will take time until the final decisions are made, and patients can receive modern and effective treatment in these countries. For this reason, Biotherapy International has established branches in countries where cell therapy can be accomplished on a compassionate basis due to lack of other available therapeutic modalities.
Our Patents and Scientific Publications
Biotherapy International’s research activities have resulted in four patents and several scientific publications.
1) Methods, systems and compositions for neuronal differentiation of multipotent stem cells.
This therapy was designed to replace missing or damaged cells and tissues of the nervous system and restore its functions. Multipotent neuronal stem cells could be used in various degenerative and inflammatory diseases of the nervous system, including the central nervous system and spinal cord injuries also including stroke.
https://patents.justia.com/patent/10421961
2) MicroRNA for the generation of astrocytes
This is a method to create a population of astrocytes (auxiliary tissue of the brain) that can be used to treat certain brain disorders. Astrocytes are star-shaped glial cells found around neurons and in the areas of contact between two neurons. This type of nervous system cell carries nutrients from the blood to the neurons and is key to the functioning of the brain.
https://patents.justia.com/patent/10034902
3) Generation of neural stem cells and motor neurons A
This is a method to create neural stem cells or motor neurons. Motor neurons in the spinal cord, which innervate skeletal muscle, originate from neuroepithelial cells in a limited area of the developing spinal cord (neural tube). These motor neurons cannot renew, so any loss or degeneration usually causes fatal or irreversible neurological conditions, including paralysis or disorders such as childhood spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) in adults.
The method is used to treat a variety of neurological disorders, including multiple sclerosis, Parkinson’s disease, ALS, Alzheimer’s disease, spinal cord injury, and stroke.
https://patents.justia.com/patent/9803175
4) Methods for obtaining oligodendrocytes and their cell populations
Oligodendrocytes are a type of auxiliary cells in the nervous tissue that produce myelin. Their main function is to create the myelin sheath that protects the neurons. As such, oligodendrocytes are the cells required to treat diseases like multiple sclerosis that result in demyelinating lesions in the central nervous system and oligodendrocytes are the cells needed to repair the damage by induction or re-myelinization.
https://patents.justia.com/patent/9783781
5) Mesenchymal stem cells for vitro modeling and cell-based therapy of human diseases and banks thereof
A method of qualifying a mesenchymal stem cells (MSC) population being associated with a brain disease.
US patent number US2015/0024966A1
Our Scientific Publications
- 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.
- 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.
