Your browser does not allow saving data (e.g. private mode): bookmarks will be lost when the tab closes.
Search PubMed
Keywords, author, journal, years — results from PubMed, abstracts with Russian translation, bookmarks in your browser.
Found: 5 474
Page 256 of 548-
Classics never get old: neurotransmitters shape human cortical interneuron migration.
While key developmental functions of neurotransmitters have been described in rodent neural progenitors, there is a lack of understanding of their roles in the human fetal brain. A new study published in The EMBO Journal demonstrates that human cortical interneurons that are moving in fused brain organoids express a large repertoire of neurotransmitter receptors whose activation fine tunes selective migration strategies.
-
Hypes and Hopes of Stem Cell Therapies in Dentistry: a Review.
One of the most exciting advances in life science research is the development of 3D cell culture systems to obtain complex structures called organoids and spheroids. These 3D cultures closely mimic in vivo conditions, where cells can grow and interact with their surroundings. This allows us to better study the spatio-temporal dynamics of organogenesis and organ function. Furthermore, physiologically relevant organoids cultures can be used for basic research, medical research, and drug discovery. Although most of the research thus far focuses on the development of heart, liver, kidney, and brain organoids, to name a few, most recently, these structures were obtained using dental stem cells to study in vitro tooth regeneration. This review aims to present the most up-to-date research showing how dental stem cells can be grown on specific biomaterials to induce their differentiation in 3D. The possibility of combining engineering and biology principles to replicate and/or increase tissue function has been an emerging and exciting field in medicine. The use of this methodology in dentistry has already yielded many interesting results paving the way for the improvement of dental care and successful therapies.
-
Guided and unguided neural organoids play complementary roles in studying neurodevelopment and neuroinflammation.
OBJECTIVE: This study aimed to compare guided dorsal forebrain neural organoids with unguided neural organoids, focusing on differences in structural organization, cellular composition, and functional properties. METHODS: Using the same human induced pluripotent stem cell line, we applied two established differentiation protocols in parallel to generate guided and unguided neural organoids. RESULTS: Guided neural organoids exhibited reproducible cytoarchitecture, relatively homogeneous morphology, and robust network activity, making them particularly well-suited for modeling specific aspects of cortical neurodevelopment and neurodevelopmental disorders. In contrast, unguided neural organoids displayed greater heterogeneity in morphology and cellular composition, including prominent development of astrocytes, microglia, and choroid plexus-like structures that respond to inflammatory stimuli, positioning them as valuable models for studying neuroinflammation during brain development. CONCLUSION: These findings emphasize the importance of selecting neural organoids protocols based on specific research questions, and suggest that the guided and unguided approaches can complement each other to provide insights into neurodevelopmental and neuroinflammatory processes.
-
Beyond the mouse: organoids, spheroids, and organs-on-chips as the (inevitable) future of malaria research?
Malaria remains a major global health threat, causing substantial clinical and socioeconomic burdens in endemic regions. Despite important advances in control strategies, progress is increasingly challenged by antimalarial drug resistance, widespread insecticide resistance, diagnostic escape, and adaptive changes in vector behavior. In this context, robust experimental models are essential to improve understanding of parasite biology, host-pathogen interactions, and therapeutic responses. Murine malaria models remain central to preclinical research because they are accessible, genetically tractable, cost-effective, and well suited to controlled studies of immunity, pathophysiology, transmission, and drug efficacy. Continuous refinement of these models through parasite and host genetic engineering, including transgenic parasites and modified or humanized mouse strains, has further expanded their experimental value. However, murine models do not fully reproduce human malaria. Key interspecies differences in parasite biology, antigenic variation, cytoadherence, tissue tropism, placental structure, blood-brain barrier interactions, and disease kinetics limit direct translation, particularly for severe, cerebral, placental, and relapsing malaria caused by Plasmodium falciparum and Plasmodium vivax. These limitations underscore the need for complementary human-relevant platforms. Micro physiological systems are emerging as a critical addition to the malaria research toolbox. Spheroids offer scalable three-dimensional models for medium-throughput studies; organoids reproduce essential structural and functional features of human tissues such as the liver, brain, placenta, and vasculature; and organ-on-chip systems incorporate flow, shear stress, and multicellular interfaces to better model sequestration, endothelial activation, barrier dysfunction, liver-stage infection, and drug responses. Rather than replacing murine models, these technologies complement them by bridging the gap between reductionist in-vitro assays and human disease biology, while supporting the principles of replacement, reduction, and refinement. This narrative review examines the current landscape of murine malaria models, their major contributions and translational limitations, and the growing importance of micro physiological systems, with their limitations, in next-generation malaria research.
-
Cell-type specific defects in PTEN-mutant cortical organoids converge on abnormal circuit activity.
De novo heterozygous loss-of-function mutations in phosphatase and tensin homolog (PTEN) are strongly associated with autism spectrum disorders; however, it is unclear how heterozygous mutations in this gene affect different cell types during human brain development and how these effects vary across individuals. Here, we used human cortical organoids from different donors to identify cell-type specific developmental events that are affected by heterozygous mutations in PTEN. We profiled individual organoids by single-cell RNA-seq, proteomics and spatial transcriptomics and revealed abnormalities in developmental timing in human outer radial glia progenitors and deep-layer cortical projection neurons, which varied with the donor genetic background. Calcium imaging in intact organoids showed that both accelerated and delayed neuronal development phenotypes resulted in similar abnormal activity of local circuits, irrespective of genetic background. The work reveals donor-dependent, cell-type specific developmental phenotypes of PTEN heterozygosity that later converge on disrupted neuronal activity.
-
Characterization of mitochondrial health from human peripheral blood mononuclear cells to cerebral organoids derived from induced pluripotent stem cells.
Mitochondrial health plays a crucial role in human brain development and diseases. However, the evaluation of mitochondrial health in the brain is not incorporated into clinical practice due to ethical and logistical concerns. As a result, the development of targeted mitochondrial therapeutics remains a significant challenge due to the lack of appropriate patient-derived brain tissues. To address these unmet needs, we developed cerebral organoids (COs) from induced pluripotent stem cells (iPSCs) derived from human peripheral blood mononuclear cells (PBMCs) and monitored mitochondrial health from the primary, reprogrammed and differentiated stages. Our results show preserved mitochondrial genetics, function and treatment responses across PBMCs to iPSCs to COs, and measurable neuronal activity in the COs. We expect our approach will serve as a model for more widespread evaluation of mitochondrial health relevant to a wide range of human diseases using readily accessible patient peripheral (PBMCs) and stem-cell derived brain tissue samples.
-
How leaky is the gut in Parkinson's disease?
The intestinal epithelial barrier (IEB) plays a critical role in health and disease by regulating the absorption of nutrients, electrolytes and water while preventing gut translocation of pathogens. A compromised intestinal barrier has been reported in Parkinson's disease (PD) further reinforcing the assumption that PD is a gut-brain axis disorder and suggesting that gut-derived factors may participate in disease development and/or progression. However, the diversity of methodology between existing studies on gut permeability in PD, especially regarding the methods used for the evaluation of the IEB, has led to diverging results and it is definitely too early to draw any definite conclusions. We envision novel approaches, such as intestinal organoids and confocal laser endomicroscopy that could be used to study more precisely the IEB in PD.
-
Pluripotent stem cell-derived organoids: A brief history of curiosity-led discoveries.
Organoids are quickly becoming an accepted model for understanding human biology and disease. Pluripotent stem cells (PSC) provide a starting point for many organs and enable modeling of the embryonic development and maturation of such organs. The foundation of PSC-derived organoids can be found in elegant developmental studies demonstrating the remarkable ability of immature cells to undergo histogenesis even when taken out of the embryo context. PSC-organoids are an evolution of earlier methods such as embryoid bodies, taken to a new level with finer control and in some cases going beyond tissue histogenesis to organ-like morphogenesis. But many of the discoveries that led to organoids were not necessarily planned, but rather the result of inquisitive minds with freedom to explore. Protecting such curiosity-led research through flexible funding will be important going forward if we are to see further ground-breaking discoveries.
-
Anti-stroke biologics: from recombinant proteins to stem cells and organoids.
The use of biologics in various diseases has dramatically increased in recent years. Stroke, a cerebrovascular disease, is the second most common cause of death, and the leading cause of disability with high morbidity worldwide. For biologics applied in the treatment of acute ischaemic stroke, alteplase is the only thrombolytic agent. Meanwhile, current clinical trials show that two recombinant proteins, tenecteplase and non-immunogenic staphylokinase, are most promising as new thrombolytic agents for acute ischaemic stroke therapy. In addition, stem cell-based therapy, which uses stem cells or organoids for stroke treatment, has shown promising results in preclinical and early clinical studies. These strategies for acute ischaemic stroke mainly rely on the unique properties of undifferentiated cells to facilitate tissue repair and regeneration. However, there is a still considerable journey ahead before these approaches become routine clinical use. This includes optimising cell delivery methods, determining the ideal cell type and dosage, and addressing long-term safety concerns. This review introduces the current or promising recombinant proteins for thrombolysis therapy in ischaemic stroke and highlights the promise and challenges of stem cells and cerebral organoids in stroke therapy.
-
Efficient Gene Expression in Human Stem Cell Derived-Cortical Organoids Using Adeno Associated Virus.
Cortical organoids are 3D structures derived either from human embryonic stem cells or human induced pluripotent stem cells with their use exploding in recent years due to their ability to better recapitulate the human brain in vivo in respect to organization; differentiation; and polarity. Adeno-associated viruses (AAVs) have emerged in recent years as the vectors of choice for CNS-targeted gene therapy. Here; we compare the use of AAVs as a mode of gene expression in cortical organoids; over traditional methods such as lipofectamine and electroporation and demonstrate its ease-of-use in generating quick disease models through expression of different variants of the central gene-TDP-43-implicated in amyotrophic lateral sclerosis and frontotemporal dementia.