Autologous stem cell therapy in Ukraine

November 05, 2015

In the modern market of medical services, a number of technologies which allow selecting custom-tailored cell therapy approaches for treatment of patients begin to prevail almost in all domains of medicine. This trend has been created mainly by the use of different methods of cell therapy.

Therapies using patient’s own tissues and cells in the treatment process are called “autologous”. Autologous bone marrow transplantations have been applied for decades now in the medical practice. Apparently, bone marrow stem cells play a role of the principal active component in this type of therapy.

The capability of human stem cells to multiply and reproduce itself as well as a great deal of other human body’s cells involved in sustaining the regeneration process of its organs and tissues lies at the heart of these methods. By definition, Stem Cells are rare, undifferentiated cells that can both duplicate themselves and produce differentiated cell types that constitute the various tissues or organ systems of the human body. In other words, if they can be isolated and multiplied, they can be put back into the area of the body having trouble, and the "good" cells can take over. It is important to note that at this time, it is only adult human Stem Cells that are well-enough understood that they can be reliably differentiated into specific tissue types, and that have proceeded to clinical trials.

The quantity and activity of stem cells define the capability of the human organism to make a stand against adverse effects and, consequently, predetermine its lifetime.

Possibilities for application of these technologies extend in line with development of sciences related to human stem cells. Apart from holding the cure for blood and immunological diseases (mainly for rehabilitation purposes after radio- and chemotherapy), Autologous Stem Cells transplantations are used more and more often for treatment of neurosurgical and cardiovascular diseases. The application of stem cells for treatment of such diseases as Alzheimer’s, Parkinson’s, orthopedic diseases, diabetes and a lot of other pathologies has proceeded to clinical trials.

In the US, Germany, France, Japan, Great Britain, Australia, Israel, Korea, India, Thailand and China such cellular technologies are either approved for clinical application, or are at different stages of clinical trials. For example, in the US and Canada, there are more than 70 and in Germany there are more than 20 clinics involved in practicing various methods of cell therapy (once again mainly for rehabilitation purposes after radio- and chemotherapy). In Thailand, Hong Kong, South Korea, Russia and Israel there is a range of clinics specializing solely in cell therapy methods used for treatment of different diseases.

stem cells uses

Potential uses of Stem Cells

The cost of treatment in such clinics ranges from €18,000 for one procedure up to €250,000 for the complete course. The high price is imposed by the cost of cells isolation and cultivation.

Market of Ukraine

There are more than two dozen clinics in Ukraine which offer therapy with the use of fetal cells (i.e. derived from an abortive embryo) for the purpose of so called “rejuvenation”.

In these cases, 12-15 clients monthly (per clinic) on average resort to such services, at the cost of the procedure from $12,000 to $17,000 for foreigners. In the case of autologous cells, after certain manipulations with the cells, the patients will receive it back in the form of intravenous infusions.

Below we give some useful information provided by the Ukrainian laboratory which are engaged in autologous stem cells.

Laboratory operation scheme

Isolation of cells is performed by means of positive selection (i.e. antibodies get into direct contact only with antigens located on the surface of target cells) and negative selection (antibodies trap all extraneous cells). The negative selection approach is more preferable since it is safer for cells. The selection process is realized either with the use of magnetic particles (and, correspondingly, a magnet), or by means of the rosetting technique (negative selection). Rosettes are formed with the help of proprietary “ternary antibody complexes” between red blood cells and target cells of negative selection.

Bone marrow-derived cells are cultivated and multiplied in order to achieve the required “therapeutic” quantity. In some cases, cultivation of cells is continued with the addition of growth factors which put further propagation to a more differentiated condition (cardiac myocytes, neurons, osteoblasts, antigen-present cells, etc.).

Upon completion of the cultivation stage, it is necessary to perform an expression analysis of superficial antigens in the cell culture with the purpose of evaluating cells quantity and proportion of differentiated phenotypes and its readiness for transplantation. This procedure is usually realized using a cell sorter device, intended to use different approaches to analyze expression of stem cells specific gens and to detect various infectious agents (our detection panel contains samples for 12 injections). The cells are also assessed for viability, mainly to determine activity of different caspases as markers of apoptosis.

Main important protocols for application that can offer you in Ukrainian laboratory

  1. Isolation and cultivation of adult stem cells. Isolation of cells having CD 34/133 antigens on its surface results from the need to get rid of tumor cells, if the procedure is performed for cancer patients. For the purpose of regeneration/rejuvenation, it is advised to use another method – bone marrow specimens enrichment with different types of progenitor cells. In the latter case, the cell output is much higher than when cultivating solely stem cells.
  2. Isolation and cultivation of mesenchymal cells. Apart from cells having the CD34 antigen, the bone marrow has other, no less valuable (and sometimes even more valuable) cells, viz mesenchymal. These cells can be cultivated as a “substrate/stroma/base” for stem cells also. After introducing only/not only stem cells, a sample of almost complete bone marrow, with potential regeneration capabilities much higher than those of the CD34+/133+ cell pool, will be obtained.
  3. Isolation and cultivation of immature dendritic cells. Dendritic cells are primordial antigen-present cells of the immune system in the context of fight against viruses and tumors and the immune system reaction depends on what will be provided by these cells. This procedure is called “anti-tumor immunization”.
  4. Isolation and cultivation of tumor living cells present in the bloodstream during metastasis. It is also possible to isolate tumor cells from tissues obtained during surgeries. Once the RNA is isolated from the tumor cells and reverse-transcribed (using the SMART-technology), it will be modified, multiplied and transformed back to the RNA-form, which is then used for immunization of the patient’s dendritic cells in the culture.

autologous cells

autologous stem cells ukraine

Representatives of the laboratory talk about the procedures they do

Bone marrow samples are obtained from patients, analyzed by hematologists and shipped to our lab. The isolation of cells is performed using positive and negative selection of hematopoietic progenitors, mesechymal and other adult stem cells from bone marrow aspirate. Purified cells are cultivated in different mediums (SFEM, Ex-Vivoes, Mesencult, etc.), changed every 3-4 days and supplemented with a cocktail of 5-7 growth factors during 12-15 days. The cultivation of the multiplicated cells, if needed, is prolonged up to 14-21 days. In order to obtain a culture of immature dendritic cells, we add another growth factor’s cocktail. The immunization of immature dendritic cells of autological tumor cells is realized in conformity with the (modified) procedure described by Axel Heiser (The Journal of Immunology, 2001, 166: 2953–2960). The cellular culture is than tested for the presence of PCR-positive products specific for RNA/DNA mycoplasmas, toxoplasma, HIVs, hepatitis B, C, TT, E, CMV, papilloma and herpes viruses, etc. Readiness of cells for expansion or guided differentiation is determined by expression of certain specific genes.

Based on joint agreements in the field of research and practical activity, we’ve cultivated cell samples for approximately 30 patients, aged from 43 to 78, with totally different pathologies: starting from metabolic symptom and infarcts to strokes and oncological diseases. The partnered medical centers informed the patients about the experimental and promotional nature of the action, as well as procedure-related possible risks. As a rule, the majority of patients underwent from 2 to 5 transplantations.

In the majority of cases, the patients as well as attending doctors noticed ameliorations after the cellular therapy procedures. Given the fact that all the patients were under long and constant control by their attending doctors before undergoing the transplantation of autologous cells, we can soundly assume that changes of the condition were well perceptible to their doctors. We elaborated, in close collaboration with the doctors, an individual treatment plan for every patient, taking into consideration genetic factors, forecasts, time frames for possible effects, etc. For example, patients suffering from autoimmune diseases in the beginning received mesechymal stem cells, while cancer patients received hematopoietic progenitors, combined with cellular immunization, if autologous cancer cells (or RNA) were available. Few detected side effects, caused by intake of cells, were identical to those observed in different published studies, and added up to transient fever (in case of immunotherapy), slight euphoria (1-3 days), redness and skin itch, rheum (seldom).

Materials of this article are provided by the Laboratory of Stem Cell Biology Institute of Physiology of the National Academy of Sciences of Ukraine

All materials of this article are the property of the authors!

Please contact us and we will give you the most detailed information about Autologous Stem Cells. This information will be given by experts of the Laboratory of Stem Cell (Kiev, Ukraine). Turning to us on this issue, please specify the name of the disease that requires full or preventive treatment. We wish you live long, healthy and happy life!