Zebrafish (Danio rerio) embryo extracts improve immune response, antioxidant capacity, and stress tolerance of ship sturgeon (Acipenser nudiventris)

This review presents a balanced synthesis of the efficacy-nanotoxicity window of nanomaterials-including carbon-based structures, metallic nanoparticles, and bioceramic composites-within the context of stem cell-assisted tissue engineering. It emphasizes that increases in conventional differentiation markers may not necessarily correspond to functional maturity or long-term safety. Therefore, a gradual shift from standard viability-based assays toward lineage-specific functional assessments is discussed. The nanotoxicological profile of these materials is examined across major tissue types, highlighting how similar physicochemical properties may yield beneficial or adverse outcomes depending on concentration, exposure time, and microenvironmental conditions. In bone tissue, the review considers the point at which enhanced mineralization may be accompanied by oxidative stress and mitochondrial strain. For cartilage, potential concerns related to ion and degradation product accumulation in avascular environments are addressed, including the possible induction of inflammatory signaling and hypertrophic markers such as collagen type X. In neural and cardiac applications, efforts to improve electrical conductivity are evaluated alongside potential electrophysiological alterations, including Ca2+ imbalance and rhythm disturbances at sub-cytotoxic levels. Vascular differentiation is discussed within the context of pro-angiogenic signaling and the risk of endothelial dysfunction. By comparing experimental systems ranging from 2D cultures to induced pluripotent stem cell (iPSC)-derived organoids, the review underscores the model-dependent and tissue-specific nature of nanotoxic responses. Overall, it outlines considerations for integrating physicochemical characterization with functional and metabolic endpoints to support more reliable evaluation of nanobiomaterials in regenerative medicine.

Stem cells are key for development of disease modeling and therapies. While promising, however, current application of cutting-edge hiPSC technologies is, among others, confounded by cellular heterogeneity leading to concerns about their suitability for experimental and clinical applications. Variations across donors, tissue sources, methodologies, and analytical challenges, together contribute to the observed heterogeneity. Hence, increased understanding of heterogeneity in stem cell research is essential to advance development of reliable tissue models and effective therapies. In this review, we summarize current knowledge regarding the origins of cellular heterogeneity in hiPSC-derivatives. Differentiation protocols can be improved through the application of novel media morphogens, integration with new biomaterials and physical strategies (e.g. 3D culture, mechanical stimulation). Additionally, standardization of methods and regulations for generation and application of cell lines and neo-tissues, thorough characterization, central banking, and registration of cells will reduce variation and increase experimental reproducibility. As reliable reference datasets become more abundant the continuous development of analytical tools as well as advanced application of artificial intelligence to analyze -omics datasets will become more refined. This will aid identification of different cell types in heterogeneous cell populations and key factors driving off-target differentiation. We provide recommendations for best practices throughout the stem cell research pipeline and discuss opportunities to advance broad applicability of stem cells for disease modeling and beyond through concerted efforts to improve experimental robustness and analytical accuracy. Finally, we advocate that certain heterogeneity may be essential in development of laboratory models to faithfully mimic the in vivo situation.

Rapid and reliable identification of stem cells is a critical prerequisite for regenerative medicine and quality control during cell-based therapies. We report herein a lateral flow assay capable of detecting MSCs by dual-marker recognition using CD105 and CD29 surface antibodies. The biosensing platform relies on gold nanoparticle-conjugated CD29 antibodies as signal probes and immobilized CD105 antibodies as capture agents on the test line, allowing selective MSC recognition through sandwich-type immunocomplex formation with direct colorimetric readout. A distinct red band indicated the successful detection of MSCs, while a control line ensured assay validity and reliability. The developed LFA showed a naked eye detection limit as low as 600 cells within 15 min, which agreed with the qualitative data obtained via a smartphone-based Color Grab application. Notably, the device exhibited excellent stability with no cross-reactivity with non-target cells and successfully distinguished MSCs from their differentiated lineages. Besides this, the device retained stability for up to 28 days under room temperature. Further, MSC stemness was independently validated for CD105 and CD29 by flow cytometry (FACS), which requires a minimum of ≥10 000 cells per analysis. In comparison, the developed LFA provided reliable detection at substantially lower cell numbers, highlighting its significance as a low-input, rapid, and point-of-care alternative. This user-friendly platform represents a promising tool for rapid stemness assessment of MSCs towards their quality control and clinical translation in stem cell research and regenerative medicine applications.

Advancing Hematopoietic Stem Cell Research: The Impact of Bioengineered 3D Bone Marrow Niches.

The 25th International Congress on Reproductive Biomedicine and the 20th International Congress on Stem Cell Biology and Technology, held in Iran, brought together leading global experts to discuss pioneering advances in stem cell research and reproductive medicine. Key topics included recent progress in somatic and pluripotent stem cells toward clinical applications, developments in regenerative medicine for diverse diseases, innovations in tissue engineering, the integration of artificial intelligence (AI) in biology research, and novel strategies for treating infertility. The congresses fostered collaboration and knowledge exchange across these rapidly evolving fields, highlighting the transformative potential of stem cells in regenerative medicine and their applications in reproductive health. Participation of 33 scientists from the United States, the United Kingdom, Germany, Austria, Italy, Belgium, Turkey, China, Russia, Japan, Sweden, Switzerland, Qatar, and India facilitated a rich exchange of ideas and broadened international perspectives. The insights and outcomes from these congresses are expected to shape ongoing research initiatives and clinical practices worldwide, emphasizing the importance of continued investment in these critical areas of medicine.

Advances in Oral Cavity Stem Cell Research Revealed through Multi-omics Analysis.

The replenishment of specialized cells depends on the activity of stem cells. Recent advances in stem cell research have shown that the germline stem cells (GSCs) in Drosophila melanogaster can increase their mitotic activity in response to mating. Here, we show that this ability to respond to mating is eliminated if the males are mutant for either of the ABC transporters, White (W), Brown (Bw) or Scarlet (St), which are known for their role in eye pigmentation and amine production. However, reducing the expression of w specifically from the germline cells also caused a failure to increase GSC mitotic activity upon mating, suggesting that w is required intrinsically in the stem cells. The w gene is a common genetic background for genetic experiments and frequently used as a control. Our findings underline the importance of careful experimental design and control choice.

Molecular targeted therapies, omics, and AI based theranostics approaches for the treatment of prostate cancer.

Organoid models in viral hepatitis, primary liver cancer, and non-alcoholic fatty liver disease: Advances and challenges.

The tensions between scientific advancement and moral applications of legislation are at the political forefront of the polarizing nature of the United States. As the Supreme Court of the United States proceeds to forego stare decisis in different fields of the law, states have been delegated more power to implement restrictive laws. Notably, the Supreme Court of the United States held in Dobbs that laws regulating abortion are under the purview of state legislation. Subsequently, the Alabama Supreme Court held in LePage v. Center for Reproductive Medicine P.C. that frozen extrauterine embryos be given the constitutional guarantees of children—removing their previous classification as property. Thus, research and the utilization of in vitro fertilization encompassing embryos have halted in the state. Additionally, the United States has failed to implement federal legislation regarding the regulation of human embryonic stem cell research. Instead, the Dickey-Wicker Act prevents federal funding from being granted for research relating to human embryonic stem cells. Further, the Leahy-Smith America Invents Act prohibits the ability for claims encompassing embryos from being patented. As scientific technology advances, the utilization of a federal policy to provide regulation and transparency to American citizens is necessary as a way to incentivize the creation of life-saving medications and scientific advancements through the ethical use of human embryonic stem cells. Currently, the lack of a federal scheme creates ambiguity and risks to the advancement of and right to science.

John Gurdon was a towering figure in developmental biology, respected and admired throughout the world. His discovery, made when he was a PhD student, that the nuclei of differentiated cells retain their pluripotency was fundamental to stem cell research and regenerative medicine, and his career-long loyalty to Xenopus laevis as an experimental organism was a constant inspiration to the field. Although Xenopus has sometimes been written off as a model organism in favour of other species, it is probably true that we have learned more about early vertebrate development from its use than from that of any other species. John received many awards for his research, including the Nobel Prize in Physiology or Medicine, the Albert Lasker Basic Medical Research Award, and both the Copley Medal and the Royal Medal of the Royal Society. He was also a significant contributor to UK science infrastructure and to academic life more broadly. Not only did he co-found the institute that now bears his name, but he also served as a Governor of the Wellcome Trust, and of Eton College, as Master of Magdalene College, University of Cambridge, as President of the British Society for Cell Biology and as Chair of The Company of Biologists, the publisher of this journal. Few biologists in the UK have achieved so much or been so influential.

Investigating single-cell dynamics and morphology in tissues and embryos requires highly accurate quantitative analysis of microscopy images. Despite significant advances in the field of bioimage analysis, even the most sophisticated segmentation and tracking algorithms inevitably produce errors (e.g. : over segmentation, missing objects, miss-connected objects). Although error rate may be small, their propagation throughout a time-lapse sequence has catastrophic effects on the accuracy of tracking and extraction of single cell parameters. Extracting single cell temporal information in the context of tissue/embryo requires thus expert curation to identify and correct segmentation errors. In the movies commonly used in developmental biology and stem cell research, both the number of imaged cells and the duration of recording are large, making this manual correction task extremely time-consuming. This has now become a major bottleneck in the fields of development, stem cell biology and bioimage analysis. We present here EpiCure (Epithelial Curation), a versatile tool designed to streamline and accelerate manual curation of segmentation and tracking in 2D movies of large epithelial tissues. EpiCure uses temporal information and morphometric parameters to automatically identify segmentation and tracking errors and provides user-friendly tools to correct them. It focuses on ergonomics and offers several visualization options to help navigating in movies of tissue covering a large number of cells, speeding up the detection of errors and their curation. EpiCure is highly interoperable and supports input from a wide range of segmentation tools. It also includes multiple export filters, enabling seamless integration with downstream analysis pipelines. In this paper, using movies from several animal models, we highlight the importance of curating cell segmentation and tracking for accurate downstream analysis, and demonstrate how EpiCure helps the curation process for extracting accurate single cell dynamics and cellular events detection, making it faster and amenable on large dataset.

Breast cancer remains the most commonly diagnosed malignancy among women worldwide. Standard treatment often involves mastectomy, followed by chemotherapy and/or radiation. Approximately 40% of patients undergo breast reconstruction to address the physical and psychological effects of tissue loss. Since the first autologous breast reconstruction described in 1887, both autologous and alloplastic techniques have evolved significantly to improve patient outcomes. However, current approaches are limited by issues such as the inability to restore biological breast function, suboptimal tissue integration, and concerns over long-term implant viability. Tissue engineering has emerged as a promising field capable of overcoming these limitations. Since the 1990s, advances in biomaterials, stem cell research, and regenerative strategies have enabled the development of vascularized, patient-specific constructs with potential applications in both structural and functional breast reconstruction. This review provides a comprehensive overview of the evolution of breast reconstruction techniques and the integration of tissue engineering into the field. Particular emphasis is placed on tissue engineering's role in enhancing breast cancer treatment and diagnosis while also exploring future directions toward functional restoration, including lactation.

At the Wisconsin National Primate Research Center, we have identified a family of rhesus carrying the microtubule-associated protein tau ( MAPT ) R406W mutation linked to frontotemporal dementia (FTD). Rhesus induced pluripotent stem cells (RhiPSCs) derived from these monkeys present a unique opportunity for in vitro modeling and comparison with cells derived from MAPT R406W human carriers. Here, we report the development of a reproducible method to generate RhiPSCs compliant with the standards of the International Society for Stem Cell Research (ISSCR) to support in vitro modeling of FTD -MAPT R406W. Our stepwise approach identified efficient methods for fibroblast derivation, fibroblast reprogramming to RhiPSC, and RhiPSC maintenance over continued culture. To derive fibroblasts from MAPT wild type (WT) and R406W monkeys, a combination of manual processing and overnight enzymatic digestion was required to maximize the number of low passage fibroblasts available for reprogramming. Fibroblast reprogramming to RhiPSC using Sendai viral vectors versus oriP/EBNA1 episomal plasmids revealed the latter as most efficient. Electroporation conditions for oriP/EBNA1 reprogramming were optimized to maximize plasmid uptake and cell survival. Ultimately, eight RhiPSC lines were derived from 4 donor rhesus monkeys (n=2 WT, n=2 R406W; two clonal lines per donor) and fully characterized according to ISSCR standards. RhiPSC stemness and genetic stability was best maintained on mouse embryonic fibroblast feeders in Universal Primate Pluripotency Stem Cell medium, as opposed to Essential 12 medium supplemented with IWR1, which produced cytogenetic abnormalities. Rhesus neural progenitor cells were generated using a monolayer protocol and expressed PAX6 and NESTIN after 21 days of differentiation. Our reliable method will be useful to labs seeking to derive RhiPSCs for preclinical studies. Overall, the RhiPSCs generated from MAPT R406W carriers will be a critical resource for evaluating the molecular underpinnings of tau-related neurodegeneration across primate species.

This article examines the role of patient organizations as mediators between patients and researchers in stem cell research in Australia. We conducted semi-structured interviews with stem cell researchers and patient organization representatives as part of a broader project to deepen public understanding and foster more robust scientific practices in stem cell-based research and therapies. We used Habermas's Theory of Communicative Action as our theoretical framework to explore the relationships between patient organizations and researchers. Using this framework allowed the identification of two different ways of conceptualizing health and illness-one based on patients' experiences, which we call "the lifeworld," and another grounded on researchers', health professionals', and policymakers' professional perspectives, which we call "the rational system." We found that the different conceptualizations identified influenced the interactions between patients and researchers (and other professionals involved in the healthcare system). Patient organizations, then, act as articulators of patients' viewpoints in this scenario, which can have advantages and disadvantages. We also found that researchers need to develop less transactional forms of communication with these organizations and that policymakers and regulators could benefit from developing guidelines to encourage researchers to use diverse strategies to engage more meaningfully with patients at individual and organizational levels.

Genome editing has emerged as a transformative approach for understanding and treating retinal degenerative diseases. Combining this technology with pluripotent stem cells provides an ideal platform for modeling human development and disease, and investigating emerging therapeutic strategies ultimately aimed towards in vivo correction. This approach enables both functional studies to understand retinal degeneration and the early development of targeted therapies for inherited disease. This review offers a comprehensive overview of genome-editing techniques and the ability to create new clinically relevant models to understand human disease in retinal research, focusing on the use of the CRISPR-Cas9 system in induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), as well as highlighting recent advancements in base and prime editing. Gene editing in various retinal diseases is discussed in context of studies focusing on disease modeling or developing therapeutic strategies. Continued refinement of these techniques will be essential for advancing translational applications in retinal disease treatment.

The 3Rs are guiding principles that must be followed when designing studies and conducting toxicity research. There is ongoing controversy regarding the use of animals in research. Moreover, the European Union outlawed animal experimentation in cosmetic products on 11 March 2013. More recently, the FDA Modernization Act 2.0 removed the requirement to use animal studies as part of the process for obtaining a licence for a biological product. These moral, ethical, and legal constraints have increased the need for alternative testing procedures. 3D cell cultures have gained popularity in recent years. Small microfluidic platforms known as "organs-on-chips" are dynamic cell cultures that mimic specific microenvironments. These microchips allow scientists to collect in vivo-like data. Organs-on-chips are considered a promising replacement for animal testing, and toxicity research is rapidly adopting this novel approach, much like other scientific fields, such as neuroscience, stem cell research, and cancer investigations. Therefore, the purpose of this review is to discuss the areas of toxicology where these platforms are currently being used, summarise the most recent toxicological applications of the aforementioned platforms, discuss the opportunities and challenges they present for toxicological research, and explore the interdisciplinary approaches applied within the field of toxicology.

In the field of regenerative medicine, stem cell therapeutic development has emerged as a key technological area. Since the establishment and characterization of human embryonic stem cell lines by James Thomson in 1998, stem cell research has expanded rapidly, accelerating industrialization through the strategic protection of intellectual property (IP) rights. As technological specialization and clinical trial expansion have progressed-particularly since 2015-the feasibility of commercialization has increased. However, IP analyses in the stem cell field have largely been limited to fragmented patent trend studies. This study analyzed the characteristics and limitations of stem cell-based IP and examined the correlations among scientific publications, patent activity, and clinical trials by stem cell type from 2000 to 2020. The findings revealed significant differences among stem cell categories. In particular, adult stem cells (ASCs) demonstrated strong positive correlations between patent filings and SCI-indexed publications (R2=0.947), as well as between patent activity and clinical trials (R2=0.945), suggesting a high level of technological maturity and translational potential. In contrast, embryonic and induced pluripotent stem cells showed relatively weaker correlations. The results indicate that ASC-based IP is closely associated with clinical development and commercialization potential. This study provides strategic insights into the potential for proactive commercialization based on the importance of patents in the stem cell therapeutic industry.

Introduction: Cardiac arrest (CA) is a leading cause of global morbidity and mortality, often resulting in severe hypoxic-ischemic brain injury. Neural stem cell (NSC) therapy is a promising strategy to restore neural function after brain injury, however, major challenges remain, including functional integration of NSCs into injured brain tissue post-transplantation. Using the emerging metabolic glycoengineering (MGE) technique to chemically modify surface glycans, the non-natural, thiol-modified ManNAc analog TProp enhances cell-cell interactions, survival signals, and immune evasion for effective brain repair. The Wnt/β-catenin signaling pathway plays a pivotal role in regulating cell survival and differentiation. This study aims to evaluate TProp’s effects on brain recovery and Wnt/β-catenin pathway modulation on MGE-mediated neuroregeneration. Methods: Wnt signaling proteins in NSCs treated with PBS, TProp, and TProp+IWR-1 (Wnt signaling inhibitor) were assessed in vitro via immunofluorescence staining. Wistar rats were randomized to receive TProp-NSCs or TProp-NSC+IWR-1 (n = 6, 4 × 105 cells in 10 µL PBS) delivered via intracerebroventricular (ICV) administration 3 hours post-CA. Neurological recovery was evaluated via neurological deficit scores (NDS). The brain sections were stained using Fluoro-Jade C (FJC) to assess degenerating neuron levels. Results: β-catenin and GSK-3β expression were upregulated in TProp-NSCs, indicating Wnt pathway activation in vitro, whereas Wnt inhibition with IWR-1 reverses the upregulation. ICV transplantation of TProp-NSCs following CA significantly improved neurological scores, whereas Wnt inhibition reduced these benefits. Hippocampal FJC positive area percentage of the TProp-NSC group exhibited significantly reduced neuronal degeneration compared to the TProp-NSC + IWR group. Conclusions: This study signifies Wnt pathway activation in neuroprotection enabled by MGE, suggesting that TProp enhances neuroprotective effects via Wnt/β-catenin signaling, revealing a promising strategy to improve stem cell-based therapies for ischemic brain injury after CA. Supported in part by the R01NS125232 and R01NS110387 from the National Institute of Neurological Disorders and Stroke and 2024-MSCRFD-6401 from the Maryland Stem Cell Research Fund (all to X Jia).