Vol 18, No 3 (2023)

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.

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.

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.