Transplantation of various types of stem cells as a possible therapy for stroke has been tested for years, and the results are promising. Recent investigations have shown that the administration of the conditioned media obtained after stem cell cultivation can also be effective in the therapy of the central nervous system pathology (hypothesis of their paracrine action). The aim of this study was to evaluate the therapeutic effects of the conditioned medium of hiPSC-derived glial and neuronal progenitor cells in the rat middle cerebral artery occlusion model of the ischemic stroke. Secretory activity of the cultured neuronal and glial progenitor cells was evaluated by proteomic and immunosorbent-based approaches. Therapeutic effects were assessed by overall survival, neurologic deficit and infarct volume dynamics, as well as by the end-point values of the apoptosis- and inflammation-related gene expression levels, the extent of microglia/macrophage infiltration and the numbers of formed blood vessels in the affected area of the brain. As a result, 31% of the protein species discovered in glial progenitor cells-conditioned medium and 45% in neuronal progenitor cells-conditioned medium were cell type specific. The glial progenitor cell-conditioned media showed a higher content of neurotrophins (BDNF, GDNF, CNTF and NGF). We showed that intra-arterial administration of glial progenitor cells-conditioned medium promoted a faster decrease in neurological deficit compared to the control group, reduced microglia/macrophage infiltration, reduced expression of pro-apoptotic gene Bax and pro-inflammatory cytokine gene Tnf, increased expression of anti-inflammatory cytokine genes (Il4, Il10, Il13) and promoted the formation of blood vessels within the damaged area. None of these effects were exerted by the neuronal progenitor cell-conditioned media. The results indicate pronounced cytoprotective, anti-inflammatory and angiogenic properties of soluble factors secreted by glial progenitor cells.

Airway and lung organoids derived from human-induced pluripotent stem cells (hiPSCs) are current models for personalized drug screening, cell–cell interaction studies, and lung disease research. We analyzed the existing differentiation protocols and identified the optimal conditions for obtaining organoids. In this article, we describe a step-by-step protocol for differentiating hiPSCs into airway and lung organoids. We obtained airway and lung organoids from a healthy donor and from five donors with cystic fibrosis. Analysis of the cellular composition of airway and lung organoids showed that airway organoids contain proximal lung epithelial cells, while lung organoids contain both proximal and distal lung epithelial cells. Forskolin-induced swelling of organoids derived from a healthy donor showed that lung organoids, as well as airway organoids, contain functional epithelial cells and swell after 24 h exposure to forskolin, which makes it a suitable model for analyzing the cystic fibrosis transmembrane conductance regulator (CFTR) channel conductance in vitro. Thus, our results demonstrate the feasibility of generating and characterizing airway and lung organoids from hiPSCs, which can be used for a variety of future applications.

Stroke represents a significant global health burden, with a substantial impact on mortality, morbidity, and long-term disability. The examination of stroke biomarkers, particularly the oral microbiome, offers a promising avenue for advancing our understanding of the factors that contribute to stroke risk and for developing strategies to mitigate that risk. This review highlights the significant correlations between oral diseases, such as periodontitis and caries, and the onset of stroke. Periodontal pathogens within the oral microbiome have been identified as a contributing factor in the exacerbation of risk factors for stroke, including obesity, dyslipidemia, atherosclerosis, hypertension, and endothelial dysfunction. The alteration of the oral microbiome may contribute to these conditions, emphasizing the vital role of oral health in the prevention of cardiovascular disease. The integration of dental and medical health practices represents a promising avenue for enhancing stroke prevention efforts and improving patient outcomes.

Regenerative medicine is a rapidly evolving field of contemporary biomedical research that offers new therapeutic strategies for conditions previously considered untreatable. Cell therapy shows particular potential in this domain. However, rigorous biosafety measures are required in its development and clinical application. This review proposes a practice-oriented biosafety framework for cell therapy, translating key risks into operational principles: toxicity, oncogenicity/tumorigenicity/teratogenicity, immunogenicity, biodistribution; and cell product quality. For each principle, preclinical approaches and regulatory expectations are summarized. Criteria for immunological safety are addressed, including activation of innate immunity (complement, T- and NK-cell responses) and the need for HLA typing. Biodistribution assessment involves the use of quantitative PCR and imaging techniques (PET, MRI) to monitor cell fate over time. The risks of oncogenicity, tumorigenicity, and teratogenicity can be analyzed using a combination of in vitro methods and in vivo models in immunocompromised animals. Product quality assessment includes sterility, identity, potency, viability, and genetic stability, with alignment of procedures to regulatory requirements and an emphasis on quality-by-design principles to ensure safe and reproducible clinical use. Integrating toxicity and safety pharmacology data supports a balanced risk–benefit assessment and clinical trial planning.

Alzheimer’s disease is a progressive neurodegenerative disorder characterized by mitochondria dysfunction, accumulation of beta-amyloid plaques, and hyperphosphorylated tau tangles in the brain leading to memory loss and cognitive deficits. There is currently no cure for this condition, but the potential of stem cells for the therapy of neurodegenerative pathologies is actively being researched. This review discusses preclinical and clinical studies that have used mouse models and human patients to investigate the use of novel types of stem cell treatment approaches. The findings provide valuable insights into the applications of stem cell-based therapies and include the use of neural, glial, mesenchymal, embryonic, and induced pluripotent stem cells. We cover current studies on stem cell replacement therapy where cells can functionally integrate into neural networks, replace damaged neurons, and strengthen impaired synaptic circuits in the brain. We address the paracrine action of stem cells acting via secreted factors to induce neuroregeneration and modify inflammatory responses. We focus on the neuroprotective functions of exosomes as well as their neurogenic and synaptogenic effects. We look into the shuttling of mitochondria through tunneling nanotubes that enables the transfer of healthy mitochondria by restoring the normal functioning of damaged cells, improving their metabolism, and reducing the level of apoptosis.