Therapeutic efficacy of olfactory ensheathing cells and type I collagen administered separately or in combination was studied in a model of chronic spinal cord injury in rats. The introduction of collagen hydrogel at a concentration of 4 mg/ml with and without olfactory ensheathing cells into spinal cord cysts reduced cyst volume and restored hindlimb motor function. The introduction of collagen hydrogel at both concentrations (1 and 4 mg/ml) with and without ensheathing cells stimulated remyelination of damaged nerve tissue. The results show that further study of this bioengineered preparation, as well as other combinations with cells or hydrogels is promising for the treatment of spinal cord injuries.

Alzheimer’s disease was induced in female Wistar rats by bilateral injection of β-amyloid fragment 1-42 into the hippocampal region. After 8 weeks, ensheathing cells of the olfactory mucosa were transplanted into the hippocampus at the same stereotactic coordinates. These cells survived for 8 weeks; large clusters of cells were observed on week 4. On weeks 3-5 after transplantation of ensheathing cells, experimental animals demonstrated a significant cognitive improvement (memory and spatial orientation). The obtained results create prerequisites for further studies of ensheathing cells as a potential cell product for personalized therapy of Alzheimer’s disease.

A new gene-cell construct expressing nerve growth factor (NGF) has been developed. After obtaining engineered adenovectors Ad5-RGD-CAG-NGF and Ad5-RGD-CAG-EGFP, transduction efficiency and transgene expression were studied and multiplicity of infection was determined. The efficacy of transduced human olfactory ensheathing cells expressing NGF in restoring motor activity in rats has been shown in a limited period of time. Improved rat hindlimb mobility and cyst size reduction after gene-cell construct transplantation were more likely due to the cellular component of the construct.

The interaction of natural killer and trophoblast cells underlies maternal-fetal immune tolerance. The data on the participation of endoglin (ENG, CD105), or its soluble form, in the regulation of the communication of these cells are currently insufficient. In this study, we have investigated the role of endoglin in the intercellular interactions between natural killer cells and trophoblasts. Here, we show that NK-92 cells and JEG-3 cells constitutively express MICA/B, and CD105. In the presence of JEG-3 cells, the expression of NKG2D, CD94, MICA/B, and CD105 by NK-92 cells was increased, and the number of NK-92 cells expressing NKG2A, CD94, and MICA was reduced. Antibodies against ENG and recombinant endoglin (rENG), attenuated the trophoblasts’ influence and returned the phenotype of the NK-92 cells to that of cells found in monoculture conditions. The antibodies and rENG also increased the expression of pSMAD2/3 by NK cells in both monoculture and co-culture conditions. The antibodies increased the trophoblasts’ sensitivity to the cytotoxic effect of NK cells. In general, our findings indicate a significant role of endoglin in the intercellular communication between NK cells and trophoblasts. We also speculate that endoglin forms a complex with TGFβ, which aids in TGFβ trafficking between these cells.

The review considers the use of exogenous neurotrophic factors in the treatment of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and others. This group of diseases is associated with the death of neurons and dysfunction of the nervous tissue. Currently, there is no effective therapy for neurodegenerative diseases, and their treatment remains a serious problem of modern medicine. A promising strategy is the use of exogenous neurotrophic factors. Targeted delivery of these factors to the nervous tissue can improve survival of neurons during the development of neurodegenerative processes and ensure neuroplasticity. There are methods of direct injection of neurotrophic factors into the nervous tissue, delivery using viral vectors, as well as the use of gene cell products. The effectiveness of these approaches has been studied in numerous experimental works and in a number of clinical trials. Further research in this area could provide the basis for the creation of an alternative treatment for neurodegenerative diseases.

This paper shows for the first time that co-transplantation of human olfactory ensheathing cells with neurotrophin-3 into spinal cord cysts is more effective for activation of remyelination than transplantation of cells with brain-derived neurotrophic factor and a combination of these two factors. The studied neurotrophic factors do not affect proliferation and migration of ensheathing cells in vitro. It can be concluded that the maximum improvement of motor function in rats receiving ensheathing cells with neurotrophin-3 is largely determined by activation of remyelination.

BACKGROUND AND OBJECTIVES: In the context of war, rural areas of Ukraine have encountered serious environmental challenges that threaten not only the environment but also the resilience of communities. The primary aim of this study is to investigate how the implementation of circular economy principles and inclusive strategies can mitigate the risks associated with ecological threats, tackle resource utilization challenges, and promote ecological restoration in rural regions affected by conflict. The main objectives encompass evaluating the effectiveness of circular economy approaches and inclusive policies in addressing the aforementioned issues. METHODS: Diverse approaches were employed to assess the effects of circular economy and inclusivity on the environmental conditions in rural regions. The study was founded upon an extensive examination of scientific literature and a thorough analysis of prior studies. This approach facilitated the evaluation of the potential consequences of these factors on the environment. Quantitative data analysis was employed as the primary approach, utilizing regression modeling to ascertain the correlation between the degree of inclusion and the adoption of circular economy practices. This analysis further facilitated the identification of any alterations in the level of ecological threat. Additionally, the use of taxonomy allowed determining the level of ecological threaten, while cluster analysis was used to distribute territories based on the level of ecological threaten ecocide. Factor analysis was utilized to gain insights into the impact of circular economy practices and inclusion on ecological risks, while regression analysis was employed to validate the research hypotheses. FINDINGS: The study demonstrates integrating circular economy principles with active community engagement significantly mitigates ecological threats in wartime rural Ukraine, achieving a 45 percent risk reduction. Direct positive impact of circular economy practices and inclusivity on environmental health, marking a 30 percent ecological improvement, was discovered. Innovations and inclusive practices have been found to significantly enhance biodiversity, resulting in a remarkable 25 percent increase. Additionally, these advancements have also been observed to boost agricultural productivity by an impressive 20 percent. These findings underline the urgent need for a shift towards a sustainable management model combining circular economy principles with extensive social inclusion, essential for ecological resilience and rejuvenation of rural Ukrainian areas amidst conflict. CONCLUSION: Implementing circular economy and inclusivity in rural Ukraine reduces ecological threats by 45 percent, enhancing biodiversity and agricultural productivity. Circular economy and inclusion are key strategies for ensuring ecological resilience and restoration in rural areas of Ukraine during war time. The resilience and recovery of affected regions can be enhanced through the adoption of circular economy practices, waste reduction strategies, resource reuse initiatives, the advancement of low-carbon technologies, and active community participation in environmental endeavors.

We analyzed the main approaches to the modeling of Alzheimer’s disease for studying the effectiveness of cell therapy. Recent advances in regenerative medicine in the field of neuroscience create prospects for the use of various cell preparations for the treatment of Alzheimer’s disease. Experimental data on the use of neural stem/progenitor cells, mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells in various models of Alzheimer’s disease are presented. Of particular importance is the standardization of protocols. The use of a standardized protocol in modeling of Alzheimer’s disease will allow a comparative analysis of the effectiveness and safety of treatment to identify the optimal cell preparation. The data obtained on experimental animals can form the basis for further preclinical and clinical studies of cell therapy for Alzheimer’s disease.

Alzheimer's disease was modeled in female Wistar rats aged 4 months by stereotaxic bilateral injection of a synthetic peptide β-amyloid (Aβ1-42) into the hippocampus. Behavioral tests (open field, Y-maze, passive avoidance, and Morris water maze) revealed significant impairment of memory and spatial navigation 8 weeks after β-amyloid administration. At this term, the cognitive impairments typical of Alzheimer's disease are reproduced. The experimental model of Alzheimer's disease proposed by us can be used in preclinical studies of drugs for the treatment of this pathology.

The review focuses on the most important areas of cell therapy for spinal cord injuries. Olfactory mucosa cells are promising for transplantation. Obtaining these cells is safe for patients. The use of olfactory mucosa cells is effective in restoring motor function due to the remyelination and regeneration of axons after spinal cord injuries. These cells express neurotrophic factors that play an important role in the functional recovery of nerve tissue after spinal cord injuries. In addition, it is possible to increase the content of neurotrophic factors, at the site of injury, exogenously by the direct injection of neurotrophic factors or their delivery using gene therapy. The advantages of olfactory mucosa cells, in combination with neurotrophic factors, open up wide possibilities for their application in three-dimensional and four-dimensional bioprinting technology treating spinal cord injuries.

A gene-cell construct based on rat olfactory mucosa ensheathing cells transduced with an adenoviral vector encoding a mature form of brain neurotrophic factor (mBDNF) was transplanted into post-traumatic cysts of rat spinal cord. Transplantation of the gene-cell construct improved motor activity of the hind limbs and reduced the size of cysts in some animals. How-ever, comparison of the effects of transduced and non-transduced ensheathing cells revealed no significant differences. In parallel in vitro experiments, a decrease in the proliferation of transduced cells compared to non-transduced cells was observed. It is likely that mBDNF reduces proliferation of transduced cells, which can affect their efficiency. The therapeutic efficacy of the new gene-cell construct is most likely provided by the cellular component.

Posttraumatic spinal cord cysts are difficult to treat with medication and surgery. Gene-cell therapy is a promising area of treatment for such patients. However, optimal gene-cell construct for this therapy has not been developed. We investigated the therapeutic efficiency of human olfactory ensheathing cells (OECs) transduced by adenoviral vector encoding the mature form of brain-derived neurotrophic factor (mBDNF) in spinal cord cysts. The adenoviral vectors Ad5/35-CAG-mBDNF and Ad5/35-CAG-Fluc were constructed. Spinal cysts were modeled in female Wistar rats. We selected animals at the early and intermediate stages of recovery with scores to 13 according to the Basso, Beattie and Bresnahan (BBB) scale. The efficiency of therapy was evaluated by BBB tests. No cytotoxicity was detected using the Resazurin/AlamarBlue assay for both vectors at multiplicity of infection (MOIs) of 1, 5, and 25. There was an increase in the proliferation of cells treated with Ad5/35-CAG-mBDNF at MOIs of 5 and 25. The hind limb mobility after the transplantation of Ad5/35-CAG-mBDNF- and Ad5/35-CAG-Fluc-transduced human OECs and nontransduced OECs had approximately the same tendency to improve. Cyst reduction was observed with the transplantation of all the samples. Although Ad5/35-CAG-mBDNF-transduced OECs had high BDNF expression levels in vitro, these cells lacked positive effect in vivo because they did not exhibit significant effect concerning functional test when comparing the groups that received the same numbers of OECs. The therapeutic efficiency of transduced OECs appears to be due to the cell component. The autological and tissue-specific human OECs are promising for the personalized cell therapy. It is extremely important to test new gene-cell constructs based on these cells for further clinical use.

The regeneration of nerve tissue after spinal cord injury is a complex and poorly understood process. Medication and surgery are not very effective treatments for patients with spinal cord injuries. Gene therapy is a popular approach for the treatment of such patients. The delivery of therapeutic genes is carried out in a variety of ways, such as direct injection of therapeutic vectors at the site of injury, retrograde delivery of vectors, and ex vivo therapy using various cells. Recombinant adenoviruses are often used as vectors for gene transfer. This review discusses the advantages, limitations and prospects of adenovectors in spinal cord injury therapy.

In this study, we identified the optimal time frame for the development of signs of beta-amyloid-induced Alzheimer's disease using behavioral tests. It was shown that significant cognitive impairments in males were observed 8 weeks after injection of the beta-amyloid peptide.

We developed a viral vector Ad5/35-CAG-mBDNF expressing the mature form of BDNF (mBDNF). On the basis of olfactory ensheathing cells transduced with this adenovector, a new gene-cell construct was obtained. In experiments in vitro, high viability of the transduced olfactory ensheathing cells and enhanced secretion of BDNF by these cells were observed. It is possible that a new gene-cell construct will significantly increase the regenerative effects of transplanted olfactory ensheathing cells.

Neurotrophin-3 enhances the effectiveness of human olfactory ensheathing cells in improving hind limb mobility in rats with post-traumatic cysts of the spinal cord. Transplantation of olfactory ensheathing cells into spinal cord cysts reduced their size; neurotrophin-3 did not modulate this effect. Combined preparation of human olfactory ensheathing cells and neurotrophin- 3 can be used in neurosurgery for the treatment of patients with spinal cord injuries.