Vol 15, No 4 (2020)

The material contains a conversation between doctors-developers, administrators and clinicians on the introduction of banking of umbilical cord blood and umbilical cord cells into healthcare practice. The data on clinical studies conducted in the world to assess the safety and effectiveness of the use of umbilical cord blood cells are presented.

The novel coronavirus SARS-CoV-2 has caused a life-threatening disease COVID-19 provoked a pandemic over the world. The effectual host immune response including innate and adaptive immunity against SARS-Cov-2 seems crucial to control and resolve the viral infection. However, the severity and outcome of the COVID-19 might be associated with the excessive production of pro-inflammatory cytokines "cytokine storm” leading to an acute respiratory distress syndrome. Regretfully, the exact immunophysiology and treatment, especially for the severe COVID-19, is still uncertain. Novel therapeutic strategies are urgently needed to eliminate the viral reservoir in the host. In this review, we described several potential strategies for immunotherapy to cure SARS-CoV-2 infection. This may provide clue of using immune therapy as combine treatment to prevent the patient develop into severe respiratory syndrome and largely reduced complications.

Gene-activated bone grafts and substitutes are promising tools for the bone defect healing, which are capable to induce prolonged production of growth factors with a therapeutic effect at physiological concentrations. Non-viral methods of delivering plasmid constructs with target genes are the safest for clinical use, but their efficiency is lower in comparison with viral vectors. To solve the problem of plasmid delivery into cells, some systems with a high transfection capacity and ensure sufficient cell viability are being developed. Moreover, there are different approaches to improve the level of expression of target genes and targeted delivery to the bone defect in order to achieve local therapeutic concentrations. This review considers approaches which are aimed to increase the efficiency of bone tissue regeneration methods based on non-viral delivery systems for osteoinduction genes using the example of the bone morphogenetic protein-2 gene.

Study of postimplantation immune response to decellularized matrices has great importance for assessing biocompatibility of tissue-engineered structures based on them, since inflammatory process and excessive production of inflammatory mediators lead to complications and implant rejection. The aim of this research: serum cytokine profile studying after subcutaneous implantation of decellularized esophagus matrix in rats. Experimental data were obtained on male Wistar rats aged 5-6 months (n=55). Rats were divided into 4 groups: two control groups, experimental and comparison group. Control group 1 consisted of conditionally healthy rats (n=10), control group 2 - shame-operated animals (incision in scapula without implantation, n=15). In experimental group (n=15), rats underwent subcutaneous implantation of decellularized esophagus fragments; in group 2 (n=15) - native esophagus fragments. Peripheral blood sampling and fragment explantation were performed on 7th, 14th and 21st experimental days. Serum samples were tested for IL1a, IL2, IL4, IL17A, TNFa, IFNy, GM-CSF content by ELISA. Explanted native esophagus and decellularized esophagus fragments were subjected to histological analysis. On 7th experimental day, significant increase in IL1 a content was observed in rats with implantation of decellularized esophagus fragments. IL17A, IFNy, GM-CSF content significantly decreased. On 14th day, IL17A concentration sharply decreased in comparison with value on 7th experimental day and control 1. IL1 a and IFNy concentration decreased in comparison with control group 1 values and 7th day respectively. On 21st day, dynamics of decrease in IL17A, IFNy, IL1 a content in this rat group was revealed. Thus, it was found change in concentrations of studied cytokines corresponds to regeneration histomorphological picture in group that underwent implantation of acellular matrices against of active inflammatory reaction in comparison group. Concentrations of IL1 a, IL4, IL17A, IFNy reflect positive dynamics of wound healing process and absence of decellularized matrix rejection.

Traumatic injuries of peripheral nerves lead to profound disability in patients with partial or total loss of limb function. There remains the question about the use of technologies for detecting defects of the peripheral nerve with concurrent of its regeneration. In the study it has been investigated the effect of the gene-therapeutic plasmid construct pBud-VEGF165-FGF2 with various methods of overcoming 5 mm diastasis of the sciatic nerve: nerve autograft and tubulation with the NeuraGen® tube. In the study groups, assessment of sciatic nerve regeneration was based on functional and morphometric parameters. Direct injection of plasmid pBud-VEGF165-FGF2 stimulates regeneration and restoration of motor function in both groups, but with different efficacy. Comparative analysis of nerve defect replacement in combination with direct gene therapy showed the most effective approach with autologous insertion replacement by comparison to the NeuraGen. Thus, on the basis of the obtained data, we can assert that nerve autograft of the peripheral nerve remains the "gold standard” and provides the best hope of research in combination with the use of various regeneration stimulants.

Treatment ofprognostically unfavorable forms ofacute leukemia isaserious problem ofhematology, since their frequency inthe group ofadult patients reaches 60%, and inelderly patients- 80-90%.Aim: toanalyze the case ofdiagnostics and treatment ofacute myelomonoblastic leukemia with anunfavorable genetic prognosis inayoung adult female using double haploidentical bone marrow transplantation.Samples ofbone marrow and peripheral blood ofpatient K., 35years old, who recived program chemotherapy and double haploidentical bone marrow transplantation inthe Sverdlovsk Regional Hematological Centre were examined.Atthe onset ofdisease was noted hyperleukocytosis, blastaemia and infiltration ofleukemic cells inthe bone marrow. Cytochemical reactions tolipids were positive in7,0% ofblasts, small-granular and large-granular glycogen was detected in24,0% ofblast cells, and diffuse- in22,0%. Immunophenotypically, 28,0% ofblast cells were characterized byexpression ofHLA-DR, CD13, CD33, CD34, CD38, CD117, MPO-cyt, 13,0%- CD33, CD11cyt, CD64, CD14. The cytogenetic study determined the karyotype 48, XX, +4, +21[2]/ 47, XX, +4[3]/ 46, XX[2]. Non-synonymous transversions с. 2447A>Тinс-KIT gene, с.215С>GinТР53, and transition с. 2644С>ТinDNMT3A were detected using direct sequencing method. Despite the detection ofoncogenic mutations, the tumor was chemosensitive topolychemotherapy (including anthracyclines with cytarabine). However, given the unfavorable genetic prognosis, itwas decided toperform abone marrow transplantation. Due tothe lack ofanHLA-matched unrelated donor, the first haploidentical transplantation was performed from the patient'seldest daughter. At+51day, transfusion ofdonor white blood cells with correction ofthe immunosuppression scheme was performed tocorrect persistent pancytopenia. At+ 71day after the first transplantation, taking into account the remaining pancytopenia, asecond haploidentic transplantation from the patient'syounger daughter was performed. The total duration ofhematological remission was 48months, including 36months after the second haploidentical bone marrow transplantation.

Umbilical cord blood is a unique source of hematopoietic cells for transplantation in hematological diseases and other socially significant pathologies. The development of regenerative medicine requires clear protocols governing the use of umbilical cord blood and its components (cells, plasma) in clinical practice. In the Russian Federation, today, there is no proper regulatory framework for working with umbilical cord blood and its components, which is a limiting factor in the development of cellular technologies and regenerative medicine in general. The article analyzes the legal framework for regulating the use of umbilical cord blood and its components in the Russian Federation and abroad - the countries of the European Union and America.