DEVELOPMENT AND INTRODUCTION INTO CLINICAL PRACTICE A PERSONALIZED CELL TRANSPLANT WITH HIGH REGENERATIVE POTENTIAL FOR RECOVERY AND REPLACEMENT THERAPY OF LOST FUNCTIONS OF ORGANS AND SYSTEMS BASED ON GENE AND CELL TECHNOLOGIES

within the framework of the implementation of the scientific and technical program “National program for the introduction of personalized and preventive medicine in the Republic of Kazakhstan”

Relevance

The scientific novelty and significance of the task of developing gene, cell technologies and regenerative medicine is that this is the basis of the medicine of the future, capable of not only completely replacing donor organ transplantation, but also saving humanity from many diseases – from restoring damaged tissues to restoring organ functions and systems. Despite the successes achieved in the world in this direction, an important point of the task is to study the fundamental mechanisms of the influence of pathological stress on the state of cells and the search for effective methods for restoring their functional and bioregulatory activity for subsequent cell transplantation of “healthy” cells.

The results of the studies performed do not sufficiently illuminate the mechanisms at the local (organ, tissue) and system levels, and the correlations between the obtained clinical effects and the associated immunological data of both cells and the immune status of the body as a whole are not convincing enough.

In this regard, the objective of this study is to develop new approaches to the generation of stem cells for the qualitative implementation of their biomedical and regeneration strategies, which includes: biotechnology of bone marrow cells and the development of optimal conditions for the restoration of a stem cell composite for transplantation; study of the stress state of bone marrow cells in conditions of chronic pathology based on the assessment of the structural and functional state of peripheral blood lymphocytes; study of the regenerative potential of hematopoietic and mesenchymal bone marrow stem cells in conditions of chronic pathology by analyzing their telomere length and telomerase activity by polymerase chain reaction (PCR); carrying out molecular genetic analysis of bone marrow stem cell cultures in pathological conditions using the microarray method (microarray) to assess the number of functionally active genes (mRNA) and, finally, the development of optimal technologies for reconstructive and restorative regulation of the process of generating multipotent mesenchymal stem cells – mechanisms of protection and remodeling/recovery of cells from the inhibitory influence and consequences of chronic stress.

As well as the study of the pathogenetic mechanisms of the positive effect of cell therapy are extremely promising and relevant for clinical cell transplantation, these are:

– study of the mechanisms of development of CHF, in particular, the study of the role of systemic inflammatory response (SIR) in the pathogenesis of dilated cardiomyopathy and the influence of autogenous mesenchymal SCs in cellular cardiomyoplasty.

– study of the regular and immunocorrective influence of BM MSCs on the course of autoimmune inflammation at the systemic and local levels in SJS and SLE, as well as the genetic prerequisites for the occurrence of these diseases in Kazakhs.

– study of the variability of daily glycemia after BM MSC transplantation, as well as the dynamics of the course of microvascular and neuropathic complications of DM.

– study of the regular influence of BM MSCs on the regression of liver fibrosis, angiogenesis processes and restoration of liver functions.

– at the present stage of the development of world science, great emphasis is given to genetic research, the results of which will open wide opportunities for the progress of personalized medicine in the future. In this regard, our development of gene and cellular technologies in medical science will for the first time open up the possibility of an optimized, individual approach in the treatment of patients with severe pathology. Gene cellular technologies and research will be directed primarily to the regulation of mRNA expression in the cells of the central organ of immunogenesis to restore protein biosynthesis by ribosomes, the functional ability of which, according to the scientific literature, is reduced in conditions of chronic pathology, which generally affects the regenerative potential of cells. That is why the task of this scientific and technical program is to study the genetic activity of stem cells, as well as the length of their telomeres and telomerase activity in conditions of a long-term chronic disease (chronic pathological stress “on the organs of immunogenesis and, above all, bone marrow cells – as the central organ of the immune systems and related disorders of the functional and bioregulatory activity of cells in the implementation of morphoregulatory functions.

Thus, the development of new methods for assessing the initial biological reserves of bone marrow cells in pathological conditions and predicting recovery processes

based on the study of gene and cell technologies, represent a very promising, extensive area, the implementation of which requires a versatile, scientific research, which actually determined the goals of this task.

The purpose of this study

To develop and introduce into clinical practice a personalized cell transplant with a high regenerative potential for restorative and replacement therapy of lost functions of organs and systems based on gene and cell technologies.

Research objectives

New approaches in the generation of stem cells for the qualitative implementation of their biomedical and regeneration strategies.
Biotechnology of bone marrow cells and development of optimal conditions for the restoration of a stem cell composite for transplantation.
Study of the stress state of bone marrow cells in conditions of chronic pathology based on the assessment of the structural and functional state of peripheral blood lymphocytes.
Study of the regenerative potential of hematopoietic and mesenchymal bone marrow stem cells in conditions of chronic pathology by analyzing their telomere length and telomerase activity by polymerase chain reaction (PCR).
Carrying out molecular genetic analysis of bone marrow stem cell cultures in pathological conditions using the microarray method to assess the number of functionally active genes (mRNA).
To study the molecular and cellular mechanisms of regulation of the recovery processes of various organs and systems during cell transplantation
To study the efficacy and safety of intracoronary use of mesenchymal autologous bone marrow cells in patients with ischemic cardiomyopathy with ejection fraction (EF≤40%).
Study of molecular and cellular mechanisms of regulation of regenerative processes of various organs and systems during cell transplantation in autoimmune diseases
Evaluation of the results of comparative treatment of patients with SLE and SJS with traditional methods of treatment and using mesenchymal stem cell transplantation with high-dose immunosuppressive therapy in the Kazakh population.
Determination of predictors of laboratory and immunological control based on the study of hematological, immunological, morphological and clinical parameters against the background of transplantation of mesenchymal stem cells of autologous bone marrow with high-dose immunosuppressive therapy in patients with SLE and SJS in Kazakh papulation
Study of molecular and cellular mechanisms of regulation of regenerative processes of various organs and systems during cell transplantation in type 1 and 2 diabetes mellitus and their complications. Transplantation of mesenchymal bone marrow cells in the treatment of diabetes mellitus and its complications
Establishment of the effect of bone marrow mesenchymal stem cell transplantation on the dynamics of ophthalmic microvascular complications (condition of the bulbar conjunctiva, fundus microcirculation) in patients with type 1 and type 2 diabetes mellitus.
Study of molecular and cellular mechanisms of regulation of regenerative processes of various organs and systems during cell transplantation in primary biliary cholangitis. Study of the effectiveness of transplantation of multipotent mesenchymal autologous bone marrow cells in the correction of autoimmune mechanisms of development of primary biliary cholangitis (continued)
Evaluation of the laboratory efficacy of multipotent mesenchymal autologous bone marrow cells in patients with primary biliary cholangitis.

Co-executor of the study: JSC “National Scientific Medical Center”.