Genes & Cells

This review discusses the mechanisms underlying the therapeutic effects and the clinical prospects of mesenchymal stromal cell (MSC) transplantation in dilated cardiomyopathy. The development of dilated cardiomyopathy is based on a complex interplay of multiple etiological factors and mechanisms. This condition is characterized by high prevalence, unfavorable prognosis, and substantial mortality, highlighting the need for innovative treatment methods. In dilated cardiomyopathy, mesenchymal stromal cells exert multifaceted effects on the injured myocardium, primarily through paracrine secretion of cytoprotective, immunomodulatory, proangiogenic, and antifibrotic factors; suppression of oxidative stress; and restoration of cardiomyocyte energy metabolism. Preclinical and clinical studies have demonstrated the ability of mesenchymal stromal cells to improve cardiac contractile function and patients’ quality of life. Sustained long-term benefits have been reported, with allogeneic cells showing greater therapeutic potential and a lower incidence of complications compared with autologous cells. To enhance the efficacy of MSC transplantation and facilitate its broader implementation in clinical practice, several challenges must be addressed, including optimization of cell sources, delivery methods, and strategies to improve cell survival within the hostile myocardial microenvironment. In this context, genetic modification of mesenchymal stromal cells aimed at enhancing their cardioprotective and regenerative properties represents a promising approach to improving outcomes in patients with dilated cardiomyopathy.

BACKGROUND: Probiotics are capable of modulating immune responses through interactions with the gut microbiota, potentially enhancing the efficacy of immunotherapy and reducing adverse effects of chemotherapy and radiotherapy. Certain probiotic strains have demonstrated the ability to suppress chronic inflammation and augment antitumor immunity; however, their clinical application requires further investigation.

AIM: This work aimed to evaluate the effects of oral administration of the probiotic strains Lacticaseibacillus rhamnosus K32 and Bifidobacterium adolescentis 150 on tumor growth and gene expression in the B16-F10 melanoma model, as well as on gut microbiota composition in experimental animals.

METHODS: The experiment was conducted in C57BL/6 mice bearing B16-F10 melanoma. Animals were divided into three groups: control (no intervention) and two experimental groups for oral administration of B. adolescentis 150 or L. rhamnosus K32, respectively. Changes in gut microbiota composition were analyzed by full-length 16S rRNA gene sequencing using Oxford Nanopore technology. The transcriptomic response of B16-F10 melanoma cells to probiotic administration was assessed by RNA sequencing.

RESULTS: Substantial differences were observed in the effects of the studied probiotic strains on B16-F10 melanoma progression. B. adolescentis 150 significantly stimulated experimental tumor growth by 29% (p_adj. = 0.02 vs. control; p_adj. = 0.001 vs. L. rhamnosus K32; adj., Bonferroni correction applied). At the molecular level, this stimulation was associated with suppression of interferon signaling, activation of proliferative pathways (WNT/β-catenin, TGF-β), and reduced expression of immune cell markers in melanoma tissue. In contrast, L. rhamnosus K32 reduced tumor growth by 18% (not significant; p_adj. = 0.4) and was associated with increased expression of cytotoxic T lymphocyte and NK cell markers, as well as activation of interferon response pathways. Both probiotic strains induced marked alterations in gut microbiota composition, characterized by an increased relative abundance of Klebsiella spp., and were associated with activation of proinflammatory signaling pathways (NF-κB, IL-6/JAK/STAT3, IL-2/STAT5) in tumor tissue. Notably, administration of both probiotics was linked to activation of epithelial–mesenchymal transition and hypoxia in the tumor, potentially creating conditions favorable for tumor progression and metastasis.

CONCLUSION: These findings highlight the complex and context-dependent effects of probiotics on tumor development and underscore the need for careful strain selection in the adjuvant therapy of melanoma and other malignancies.

BACKGROUND: The number of studies investigating physical methods of cell targeting is steadily growing. Within the field of magnetic cell targeting, two main approaches have recently emerged: the use of microscale structures as magnetic carriers, e.g, porous spheroids, helices, and microrobots, that transport cells, and the use of nano- or microscale magnetic particles that directly label cells.

AIM: The study aimed to review experimental studies on the use of magnetic particles for targeted delivery of mammalian cells in order to identify the main parameters of magnetic labeling and targeting systems.

METHODS: Scientific data was searched in the PubMed, Cochrane Library, and eLIBRARY.RU databases for the period from January 2019 to September 2024 using the keywords magnetic cell targeting, magnetic cell delivery, magnetic cell localization, and magnetic cell guidance. Original experimental in vitro and in vivo studies were included if they involved labeling mammalian or human cells with magnetic nano- or microparticles for targeted delivery using magnetic fields. Data on study design, cell lines used, characteristics of magnetic particles, magnetic labeling conditions and efficiency, characteristics of magnetic trapping systems, efficiency of magnetic delivery, and clinical effects in in vivo disease models were extracted from the selected articles.

RESULTS: A total of 62 articles were included in the analysis, of which 63% (39 studies) involved animal disease models, mainly affecting the nervous system, heart, eyes, urinary system, musculoskeletal system, and cancer. The most common labeled cells were multipotent mesenchymal stromal cells (27 studies), immune system cells (16 studies), and endothelial cells and their progenitors (7 studies). In most studies, superparamagnetic iron oxide nanoparticles were used for cell labeling (82% of studies) with more than 30 types of coatings, whereas neodymium magnets of various configurations at 0.005–1.450 T magnetic induction served as targeting systems. In 84% of studies, the optimal labeling concentration of magnetic particles ranged from 10–100 µg Fe/mL, with a labeling time of 4–24 h.

A high degree of labeled cell magnetic controllability was demonstrated in vitro. In 19 animal studies, magnetic targeting resulted in a 1.16- to 20-fold increase in local cell concentration within the target area. In 85% of in vivo studies, magnetic targeting produced a more pronounced therapeutic effect compared with controls without targeting systems. Overall, the analysis confirms the high clinical potential of magnetic targeting in cell therapy.

CONCLUSION: Magnetic targeting of cells using magnetic particles is a rapidly developing and promising technology in the field of regenerative medicine and cell therapy.