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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., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the senior authors or other co-authors who contributed their efforts to this manuscript., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

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., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

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. However, 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., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

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.

We studied the effect of transplantation of ensheathing cells obtained from the olfactory mucosa of rats and humans on the size of posttraumatic spinal cord cysts. MRI examination showed that transplantation of these cells into experimental posttraumatic cysts of the spinal cord led to a significant decrease in cyst volume and even their complete disappearance in two animals receiving transplantation of rat or human cells. These findings attested to regenerative processes developing as a result of ensheathing cell transplantation. Further studies in this field will be aimed at elucidation of the mechanisms underlying spinal cord regeneration in the area of posttraumatic cysts after transplantation of ensheathing cells.

In this work, an optimal protocol was developed for obtaining adhesion culture of neural stem/progenitor cells (NSPC) of rat olfactory mucosa. During the development of the protocol, the conditions for cell culturing on adhesion substrates fibronectin and laminin in DMEM/F-12 and neurobasal media with the same culture additives were compared. Cell proliferation was maximum during culturing on both substrates in the neurobasal medium. Using the immunofluorescence method, we found that culturing on fibronectin in the neurobasal medium ensured maximum (52.22%) content of nestin-positive cells in comparison with other culturing conditions. The highest percentage of βIII-tubulin-positive cells was detected in cultures growing on fibronectin in the neurobasal medium and in DMEM/F-12 (79.11 and 83.52%, respectively). Culturing in adhesion cultures in the neurobasal medium on fibronectin allowed obtaining cultures enriched with NSPC and neurons differentiating from them in a quantity sufficient for further transplantation. The developed protocol can be recommended for obtaining NPSC from human olfactory mucosa for the treatment of spinal cord injuries.

In experiments on rats, co-transplantation of olfactory ensheathing cells of the human olfactory mucosa and neural stem/progenitor cells from the same source into post-traumatic cysts of the spinal cord led to improvement of the motor activity of the hind limbs and reduced the size of the cysts in some animals by 4-12%. The transplantation of a combination of the olfactory mucosa cells is effective and can be used in preclinical trials for the treatment of spinal cord injuries.