News

Here you can read all news about stem cells.

Learn More

Diseases that we treat

SAFETY OF CELL THERAPY

28 March 2019

In the modern world, the issues concerning the safety of cell therapy have been incredibly relevant. But before giving a definite answer whether cell therapy is safe, one has to clearly understand what said safety implies.

When it comes to cell therapy, cancer alertness is one of the most common concerns among patients and doctors alike. In order to have a deeper insight into that matter, it is necessary to dismiss all the speculative observations of individual journalists, medical officers, and patients, and instead focus on authoritative scientific evidence. But before we start analyzing the scientific facts, let’s define the term “cell therapy”. At the moment there is a wide variety of cellular products in their pure form as well as tissue-engineered structures and surgical techniques, based on the utilizing of the ability of individual body cells to promote the regeneration process.

The most frequently used type of cells in cell therapy are the multipotent mesenchymal stromal cells (MMSCs). These cells are present in every organ and tissue of our body and act as regeneration regulators. The patient’s own tissues such as bone marrow, adipose tissue or oral mucosa are predominantly used to get MSCs and in that case, the obtained cell-based products are called autologous.

Additionally, MMSCs are immune-privileged cells, meaning they do not carry histocompatibility complex class I molecules on their surface, which makes them unrecognizable to the immune system. Thus, in cases when it is impossible to obtain the patient’s own biomaterial (contraindications to sampling, an insufficient amount of cells in the patient’s biomaterial or lack of time to prepare the cellular product in event of acute conditions), donor tissue-derived cellular products can be used [11]. Such cellular products are called allogeneic.

MMSCs are a type of adult cells capable of differentiation in various directions, including adipo-, osteo-, chondro-, neuro-, myogenic and others [1], [2], [3]. MSCs’s therapeutic effect is realized through paracrine regulation and direct influence on the surrounding cells [3]. MMSCs secrete a significant amount of cytokines, chemokines, and adhesion molecules that regulate various molecular signaling pathways by activating and/or blocking them neuro-, myogenic and others [1]. Due to paracrine signals, in particular, MSCs potentiate the survival and proliferation of endogenous cells, inhibit apoptosis, activate the differentiation of resident progenitor cells, which ultimately leads to the improved function of the damaged tissue [4],[5], [6], [7].

It was established that MMSCs are capable of influencing inflammatory processes and stimulating angiogenesis [1], [3], [8]. A large number of cytokines, produced by MMSCs, block the inflammation signals that occur during various conditions, including autoimmune processes [3], [9], [10]. It is important to note that MSCs are very easily isolated from various available sources in the human body, including bone marrow, adipose tissue, oral mucosa, umbilical cord, heart, muscles, and others [12], [13], [14], [15], [16], [17].

It was found that the properties of this type of cells are virtually identical regardless of the source [1]. However, the main and most studied MMSCs sources in an adult are bone marrow, adipose tissue, oral mucosa (gums) and placenta. Peer-reviewed publications provide evidence that cultured MSCs are vulnerable to malignant transformation and can trigger tumorigenesis [18], [19], [20]. However, if you look deeper into all the provided experiments, you will notice that they were conducted either on animal cells (mice, rats) or human cells that were genetically modified or grown using growth-promoting substances.

The case is that the process of obtaining a therapeutic dose of a cellular product takes a long time. This period of time, undoubtedly, depends on the individual specific features of the patient’s organism, their past medical history, bad health habits, and various other factors, but will eventually require at least 3 weeks. That is why many researchers and formulators try to reduce the length of the period needed to obtain the therapeutic dose of MMSCs by using numerous proliferation stimulants that accelerate cell division but at the same time may lead to changes in the cell’s properties, including oncotransformation capacity. A while back, one of the established scientific magazines published several articles, where numerous individual researchers reported the occurrence of spontaneous oncotransformation during long-term cultivation of the MMSCs [21], [22]. However, these articles were removed later and the explanatory notes added, stating that the researchers have accidentally cross-contaminated the MSCs cultures with tumor cell lines.

Thereby, there is no scientific evidence on MMSCs’s capability of spontaneous transformation when using the culture medium and serums specifically designed for MSCs expansion and implementing proper quality control of the final product.

safety of stem cells

Figure1. The geographical spread of clinical studies of MSCs-based cellular products as of February 2019.

More importantly, the safety of MMSCs is further reflected in the total number of clinical safety studies. According to ClinicalTrials.gov, there are 7670 studies registered as of February 2019. The geographical spread of said clinical studies is available in figure 1.

The main goal of any clinical trial, especially if it is conducted for cellular products, is the safety assessment.

– Published on March 28, 2019 by

Eremin Ilya Igorevich,

Vice Director for Science and Research,

MD, PhD;

Senior Research Associate at the Laboratory for Cellular Biology and Developmental Pathology at the Institute of General Pathology and Pathophysiology;

Associate Professor of the Department of Regenerative Medicine and Biomedical Technology at A.I. Yevdokimov Moscow State University of Medicine and Dentistry;

Member of the Department of Plastic and Reconstructive Surgery, Cosmetology and Cellular Technologies (Pirogov Russian National Research Medical University);

Member of International Federation for Adipose Therapeutics and Science (IFATS);

Member of International Society of Plastic & Regenerative Surgeons (ISPRES);

Member of Cell Society;

Member of International Placenta Stem Cells Society (IPLASS);

Author and co-author of more than 120 scientific articles, and co-author of 6 patents of invention.

List of literature references:

[1]. Pandey A.C., Semon J.A., Kaushal D. et al. MicroRNA profiling reveals age-dependent differential expression of nuclear factor κB and mitogen-activated protein kinase in adipose and bone marrow-derived human mesenchymal stem cells. Stem Cell Research & Therapy. 2011; 2(6): 49.

[2]. Prockop D.J. Repair of tissues by adult stem/progenitor cells (MSCs): controversies, myths, and changing paradigms. Molecular Therapy. 2009; 17(6): 939-46.

[3]. Ortiz L.A., Dutreil M., Fattman C. et al. Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. PNAS. 2007; 104(26): 11002-7.

[4]. Hung S.C., Pochampally R.R., Chen S.C. et al. Angiogenic effects of human multipotent stromal cell conditioned medium activate the PI3K-Akt pathway in hypoxic endothelial cells to inhibit apoptosis, increase survival, and stimulate angiogenesis. Stem Cells. 2007; 25(9): 2363-70.

[5]. Biehl J.K., Russell B. Introduction to stem cell therapy. The Journal of Cardiovascular Nursing. 2009; 24(2): 98-103.

[6]. Prockop D.J. “Stemness” does not explain the repair of many tissues by mesenchymal stem/multipotent stromal cells (MSCs). Clinical Pharmacology and Therapeutics. 2007; 82(3): 241-3.

[7]. Shyu K.G., Wang B.W., Hung H.F. et al. Mesenchymal stem cells are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction. Journal of Biomedical Science. 2006; 13(1): 47-58.

[8]. Da Silva J.S., Hare J.M. Cell-based therapies for myocardial repair: emerging role for bone marrow-derived mesenchymal stem cells (MSCs) in the treatment of the chronically injured heart. Methods in Molecular Biology. 2013; 1037: 145-63.

[9]. Bujak M., Frangogiannis N.G. The role of IL-1 in the pathogenesis of heart disease. Archivum Immunologiae et Therapiae Experimentalis (Warsz). 2009; 57(3): 165-76.

[10]. Van Tassell B.W., Arena R.A., Toldo S. et al. Enhanced interleukin-1 activity contributes to exercise intolerance in patients with systolic heart failure. PLoS One. 2012; 7(3): e33438.

[11]. De Miguel M.P., Fuentes-Julian S., Blazquez-Martinez A. et al. Immunosuppressive properties of mesenchymal stem cells: advances and applications. Current Molecular Medicine. 2012; 12(5): 574-91.

[12]. De Bari C., Dell’Accio F., Tylzanowski P., Luyten F. P. Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis and Rheumatism. 2001; 44(8): 1928-42.

[13]. Erices A., Conget P., Minguell J. J. Mesenchymal progenitor cells in human umbilical cord blood. British Journal of Haematology. 2000; 109(1): 235-42.

[14]. Hoogduijn M.J., Crop M.J., Peeters A.M. et al. Human heart, spleen, and perirenal fat-derived mesenchymal stem cells have immunomodulatory capacities. Stem Cells and Development. 2007; 16(4): 597-604.

[15]. In’t Anker P.S., Scherjon S.A., Kleijburg-van der Keur C. et al. Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood. 2003; 102(4): 1548-9.

[16]. Kadiyala S., Young R.G., Thiede M.A., Bruder S.P. Culture expanded canine mesenchymal stem cells possess osteochondrogenic potential in vivo and in vitro. Cell Transplantation. 1997; 6(2): 125-34.

[17]. Zuk P.A., Zhu M., Ashjian P. et al. Human adipose tissue is a source of multipotent stem cells. Molecular Biology of the Cell. 2002; 13(12): 4279-95.

[18]. Zuk P.A., Zhu M., Ashjian P. et al. Human adipose tissue is a source of multipotent stem cells. Molecular Biology of the Cell. 2002; 13(12): 4279-95.

[19]. Serakinci N, Guldberg P, Burns JS, Abdallah B, Schrødder H, Jensen T, Kassem M. Adult human mesenchymal stem cell as a target for neoplastic transformation. Oncogene. 2004 Jun 24;23(29):5095-8. DOI: 10.1038/sj.onc.1207651.

[20]. Houghton J, Stoicov C, Nomura S, Rogers AB, Carlson J, Li H, Cai X, Fox JG, Goldenring JR, Wang TC. Gastric cancer originating from bone marrow-derived cells. Science. 2004 Nov 26;306(5701):1568-71. DOI: 10.1126/science.1099513.

[21]. De la Fuente R1, Bernad A, Garcia-Castro J, Martin MC, Cigudosa JC. Retraction: Spontaneous human adult stem cell transformation. Cancer Res. 2010 Aug 15;70(16):6682. doi: 10.1158/0008-5472.CAN-10-2451.

[22]. Torsvik A, Røsland GV, Svendsen A, Molven A, Immervoll H, McCormack E, Lønning PE, Primon M, Sobala E, Tonn JC, Goldbrunner R, Schichor C, Mysliwietz J, Lah TT, Motaln H, Knappskog S, Bjerkvig R. Spontaneous malignant transformation of human mesenchymal stem cells reflects cross-contamination: putting the research field on track — letter. Cancer Res. 2010 Aug 1;70(15):6393-6. doi: 10.1158/0008-5472.CAN-10-1305. Epub 2010 Jul 14.

Patient's results of treatment
at Swiss Medica

Parkinson's disease
Autism
Lyme disease
Dementia
Multiple Sclerosis
Osteoarthritis
Diabetes type 2
Alzheimer
Kidney Disease

And what results can you get from stem cell treatment?

Fill out the form to discuss the disease and treatment options with an expert! You'll be contacted by our Medical Advisor who will collect information (medical reports, etc.) for the doctor and answer your basic questions:

1. Whether stem cell therapy will be effective in your specific case.

2. What the treatment involves.

3. How much does it cost.

CONTACT
your Medical Advisor
Please fill in all required fields.

About Swiss Medica clinic

Our primary task is to make your own cells treat your own body. We use advanced technology to activate mesenchymal stem cells derived from adipose tissue, bone marrow, etc. Donated cells can also be used. Introduced to the patient’s body, these cells help to regenerate damaged tissue. Symptoms become less obvious and/or disappear.

Follow Us

Disclaimer

*Patient feedback, articles and testimonials provided on this site are for informational purposes only and should not be considered as a guaranteed result for every case of illness. The treatment result depends on the disease, patient’s condition, number of treatment procedures, etc.

All form fields are required.