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卷 18, 编号 3 (2023)
Reviews
The modern view on adipose tissue regenerative products potential in skin pathologies treatment
摘要
At this stage of regenerative medicine development, adipose tissue as a source of stem cells is the choice option due to its availability, a sufficient number of cells and the most painless sampling procedure. The high interest in this product use in scars, wounds and other dermatological diseases treatment is driven by demonstrated positive results in other medical fields.
This review presents data on the efficacy and safety of cellular and acellular adipose tissue products use in various skin pathologies treatment. Scientific literature open electronic databases PubMed (MEDLINE), Clinical Trials, and eLIBRARY.RU were used. The literature data search was carried out using the keywords: “regenerative medicine”, “SVF”, “scar”, “skin”, “dermatology”, “nanofat”, “ADSC”, “exosomes”, “lipoaspirat”.
The article presents the results and the rationale of adipose tissue regenerative products use in the most common and most significant skin diseases treatment. Cellular and acellular adipose tissue products use in dermatology and surgery is a safe and promising direction to improve skin quality. For the subsequent effective techniques application further research is needed to assess the systemic effect, as well as the development of standardized protocols for their use.
159-172
Current approaches to the genetic modification of mesenchymal stromal cells to increase their therapeutic efficacy
摘要
One of the extensively developing innovative approaches to the treatment of socially significant diseases is the use of cell technologies based on the transplantation and co-transplantation of mesenchymal stromal cells (MSCs) or on the use of their secretome components. The interest in these cell therapies is driven by the low immunogenicity of MSCs, relative simplicity of the cell isolation and handling, a wide range of therapeutic effects and proven efficacy of reparative and immunosuppressive action thereof.
By now, more than 2,000 clinical trials on the use of MSCs or their products in various pathological conditions have been completed, with more than 200 in the last five years. Both the immunosuppressive and the regenerative effects of MSCs are mediated to a great extent by their secretome which includes chemokines, growth factors, non-coding RNAs, and other active molecules. At the same time, the degree and character of MSCs’ effects depend not only on the microenvironment or body state, but also on the characteristics of MSCs themselves, including the genetic determinants governing levels of synthesis of bioactive molecules. In this review, options of genetic modification of MSCs in order to increase their therapeutic efficacy were considered.
173-188
Modern approaches to the treatment of spinal muscular atrophy
摘要
Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease. The cause of the disease is the presence of mutations in the SMN1 gene, which leads to a decrease in the expression of the SMN protein. Decreased functional activity of the SMN protein contributes to the degeneration of motor neurons. Understanding the molecular genetic cause of spinal muscular atrophy made it possible to develop and start using Nusinersen, Onasemnogene Abeparvovec and Risdiplam drugs in clinical practice for the treatment of this disease. The main approaches to the treatment of SMA are either modifying the splicing of the SMN2 gene, which, due to a point mutation in exon 7, is unable to express the full-length SMN protein, or viral delivery of a functional copy of the SMN1 gene.
Approved drugs differ in peculiarities of use, which are associated, in particular, with the route of administration, adverse reactions and restrictions of use, including restrictions associated with the socio-economic burden of patients with SMA.
The development and use of domestic products for the treatment of SMA with a comparable clinical effect and at a lower price would reduce the cost of drug therapy for severe forms of the disease.
189-204
Analysis of the activities of cord blood banks in the Russian Federation
摘要
This review aimed to analyze the activities of all state and commercial cord blood banks in the Russian Federation, to estimate the total number of cord blood samples in storage at the beginning of 2023, and to determine the practical use of the biomaterial for treatment — allogeneic and autologous transplants for oncohematological diseases, as well as for scientific research in the field of regenerative medicine for the entire period of the banks' operation, which is twenty years.
To date, there are 12 cord blood banks providing personal, public or mixed storage of samples. At the moment, up to 26,000 cord blood samples are in public storage, and about 75,000 samples are in personal storage.
As part of the review, the main and additional services provided by banks, as well as their current cost, were studied. The average cost of cord blood sample collection in the Russian Federation is 62,500 rubles, and the average annual cost of storage is 6,000 rubles. The main market indicators, trends, key problems of biobanking and prospects for the use of cord blood cells in the Russian Federation in the coming years are considered in detail.
Separately, data on the prospects for the use of umbilical cord mesenchymal stem cells, a widely studied biomaterial, which, like cord blood, can be collected after childbirth and cryopreserved for long-term storage, are briefly presented. Stem cells of the umbilical cord are being actively studied in the field of regenerative medicine due to their properties to restore cartilaginous muscle and bone tissue, stimulate the growth of new blood vessels, and block autoimmune reactions.
In addition, the current tasks and results of the activities of Ruscord, an association of specialists and organizations in the field of procurement, storage, use of cord blood cells and cell technologies, which over several years of its activity has already made a significant contribution to the development of the biobanking market, were analyzed. In September 2020, a unified standard for the collection, processing, storage and issuance of cord blood for use was approved — the Russian standard RUSCORD.
205-218
Original Study Articles
Model of toxic fibrosis in Wistar rats: morphological and molecular-genetic parameters of the transition point to cirrhosis
摘要
BACKGROUND: To date, when studying the cellular and molecular genetic mechanisms of liver fibrogenesis in experimental rat models, no attention is paid to the transition point of fibrosis to cirrhosis as a separate stage. As this pathology develops, changes in the cell phenotype and gene expression are dynamic in nature, so it is necessary to evaluate them in a long-term temporal dynamics.
AIM: The aim of this work is to study the morphological and molecular genetic changes in the liver of Wistar rats during nodular parenchymal rearrangement.
METHODS: Fibrosis and cirrhosis of the liver in male Wistar rats was induced with a freshly prepared solution of thioacetamide, which was administered intragastrically through a tube at a dose of 200 mg/kg of body weight 2 times a week for 13 weeks. The level of mRNA of the tweak (tnfsf12), fn14 (tnfrsf12a), ang, vegfa, cxcl12 (sdf), and mmp-9 genes in the liver was detected by real-time polymerase chain reaction. Immunohistochemical study was performed on paraffin sections. α-SMA, FAP, CD68, CD206, CX3CR1, CD45 were used as markers. The area of interlobular veins and interlobular arteries was measured (µm2). The number of sinusoidal capillaries and interlobular veins was counted.
RESULTS: Based on the results obtained, it is possible to establish the transition point of fibrosis to cirrhosis as an independent separate stage of fibrogenesis. This transition was identified at stage F5, and the process itself — from F4/F5 to F6.
With the growth of fibrous tissue and nodular restructuring of the liver parenchyma, no progression of dystrophic processes and an increase in the zones of necrosis and necrobiosis of hepatocytes were noted. The number of α-SMA+ and FAP+ cells in the period F4–F5 did not change (p=0.2073 and p=0.3775, respectively). At the same time, significant F6 cirrhosis was accompanied by an increase in their number by 1.5 times (p <0.00001). Differences in the number of CD68+ cells were revealed only at the F4/F5 stage (2.0 times higher than the control, p <0.00001). The number of CD206+, CX3CR1+ and CD45+ cells remained the same. An increase in the number of interlobular veins (p <0.00001) and a decrease in sinusoidal capillaries (p <0.00001) were found compared to the control.
The transition to cirrhosis was characterized by changes in the expression levels of tweak, fn14, ang, vegfa, cxcl12, and mmp-9 mRNAs, as well as the presence and strength of the relationship between them. Significant correlations were revealed between the target genes (r=0.5–0.84; p <0.01).
CONCLUSION: The transition point of fibrosis to cirrhosis has special morphological and molecular genetic features that expand knowledge about pathomorphological changes in the liver.
219-234