Recent advancements in stem cell-derived models have significantly enhanced our understanding of human development and disease mechanisms. One notable study introduced post-gastrulation amnioids (PGAs), a 3D model derived from embryonic stem cells that accurately mimics human extra-embryonic development up to four weeks post-fertilization, thus providing a crucial tool for studying amnion formation and function (ref: Gharibi doi.org/10.1016/j.cell.2025.04.025/). In parallel, the integration of collecting systems in human kidney organoids has been achieved through a novel differentiation system that combines nephrogenic mesenchyme with ureteric bud progenitors, resulting in a functional collecting duct network (ref: Shi doi.org/10.1016/j.stem.2025.04.008/). This advancement addresses previous limitations of kidney organoids that lacked proper collecting duct structures, thereby enhancing their potential for modeling kidney diseases. Moreover, the development of a multi-kingdom genetic barcoding system, CloneSelect, allows for precise isolation of target cell clones from heterogeneous populations, facilitating the study of clone dynamics and transcriptomic landscapes (ref: Ishiguro doi.org/10.1038/s41587-025-02649-1/). Additionally, the TransEuro trial explored the transplantation of human fetal ventral mesencephalic tissue in Parkinson's disease patients, revealing both clinical benefits and challenges such as graft-induced dyskinesias (ref: Barker doi.org/10.1038/s41587-025-02567-2/). Together, these studies underscore the transformative potential of stem cell models in regenerative medicine and disease research.

Hematopoietic stem cell (HSC) research has made significant strides in understanding the mechanisms underlying HSC function and their applications in transplantation. A pivotal study demonstrated that targeted deletion of Cd47 in immunodeficient pigs resulted in long-term engraftment of human hematopoietic stem/progenitor cells, leading to robust multilineage differentiation and functional immune cell production (ref: Hu doi.org/10.1038/s41551-025-01397-6/). This finding highlights the potential of genetically engineered animal models to enhance human cell engraftment and immune reconstitution. In another study, the role of PERK signaling in maintaining HSC pool integrity under endoplasmic reticulum stress was investigated, revealing that PERK is dispensable for steady-state hematopoiesis but crucial for HSC fate regulation during stress (ref: Zheng doi.org/10.1182/blood.2024027846/). Additionally, the identification of P-selectin as a marker of aging HSCs provided insights into the mechanisms of HSC aging and its impact on blood cell production (ref: Yang doi.org/10.1038/s43587-025-00880-8/). These findings collectively advance our understanding of HSC biology and open new avenues for improving HSC transplantation outcomes.

The interplay between the tumor microenvironment and immune responses is critical for the development of effective cancer immunotherapies. A recent study identified the serotonin transporter (SERT) as a novel immune checkpoint that inhibits antitumor T cell responses. Inhibition of SERT using selective serotonin reuptake inhibitors (SSRIs) significantly enhanced T cell antitumor immunity and suppressed tumor growth in various models (ref: Li doi.org/10.1016/j.cell.2025.04.032/). This finding suggests that targeting SERT could be a promising strategy for improving cancer immunotherapy outcomes. Furthermore, the characterization of p53 dysfunction in myelodysplastic syndromes (MDS) revealed nonmutational mechanisms that may contribute to disease progression, potentially informing new therapeutic approaches (ref: Zampini doi.org/10.1200/JCO-24-02394/). Additionally, the expansion of circulating plasmablasts producing commensal-reactive IgA antibodies was identified as a predictor for chronic graft-versus-host disease (cGVHD), highlighting the importance of B cell dysregulation in post-transplant complications (ref: Habenicht doi.org/10.1182/blood.2024027301/). These studies underscore the complexity of the tumor microenvironment and its influence on immune responses, paving the way for innovative therapeutic strategies.

Research into genetic and epigenetic regulation in stem cells has unveiled critical insights into developmental processes and disease mechanisms. A comprehensive meta-analysis of genome-wide association studies on heavy menstrual bleeding (HMB) identified 36 risk loci, enhancing our understanding of the genetic architecture underlying this common condition (ref: Thibord doi.org/10.1182/blood.2024027382/). This study exemplifies the power of genetic analyses in elucidating disease mechanisms and potential therapeutic targets. Additionally, the role of human antigen R (HuR) in regulating age-related hearing loss was explored, revealing that increased levels of HuR correlate with aging in the cochlea, suggesting a potential target for therapeutic intervention (ref: Guo doi.org/10.1038/s43587-025-00860-y/). Furthermore, the integration of collecting systems in kidney organoids through the fusion of nephron and ureteric bud progenitors demonstrated the importance of developmental cues in organoid functionality (ref: Shi doi.org/10.1016/j.stem.2025.04.008/). These findings highlight the significance of genetic and epigenetic factors in stem cell biology and their implications for regenerative medicine.

Neurodevelopmental research has made significant advancements, particularly in understanding the role of neural stem cells in brain development. A study demonstrated that dopaminergic neuron progenitors derived from human pluripotent stem cells can be engineered to express immune-evasive proteins, allowing for successful engraftment in models of Parkinson's disease without immune suppression (ref: Chai doi.org/10.1016/j.stem.2025.04.004/). This breakthrough has profound implications for cell therapy in neurodegenerative diseases. Furthermore, the choroid plexus was identified as a key regulator of cerebrospinal fluid (CSF) composition during brain development, with apocrine secretion mechanisms playing a crucial role in shaping the CSF proteome (ref: Courtney doi.org/10.1038/s41593-025-01972-9/). Additionally, the establishment of dorsal-ventral patterning in human neural tube organoids using synthetic organizers provided new insights into the mechanisms governing neural development (ref: Luo doi.org/10.1016/j.stem.2025.04.011/). Collectively, these studies enhance our understanding of neural stem cell biology and its implications for developmental disorders and regenerative therapies.

The exploration of disease mechanisms and stem cell interactions has revealed critical insights into various pathologies. A functional dissection of noncoding variants associated with rheumatoid arthritis highlighted the importance of regulatory elements in disease susceptibility, paving the way for targeted therapeutic strategies (ref: Jajodia doi.org/10.1016/j.ard.2025.04.001/). Additionally, the neurodevelopmental hijacking of oligodendrocyte lineage programs by glioblastoma cells was shown to drive tumor infiltration, emphasizing the need for understanding tumor-stem cell interactions in cancer progression (ref: Wu doi.org/10.1016/j.devcel.2025.04.022/). Moreover, the expansion of plasmablasts producing commensal-reactive IgA antibodies was identified as a predictor for chronic graft-versus-host disease (cGVHD), shedding light on the dysregulation of B cell homeostasis post-transplantation (ref: Habenicht doi.org/10.1182/blood.2024027301/). These findings underscore the intricate relationships between stem cells and disease mechanisms, highlighting the potential for novel therapeutic interventions.

Organoid models have emerged as powerful tools for studying disease mechanisms and potential therapies. Bat organoids were developed to investigate antiviral responses, revealing insights into how bats can host viruses without developing disease, which may inform strategies for pandemic preparedness (ref: Kellner doi.org/10.1038/s41590-025-02155-1/). Additionally, genetic modeling of ELP1-associated Sonic hedgehog medulloblastoma identified MDM2 as a selective therapeutic target, demonstrating the utility of organoid models in cancer research (ref: Ahmad doi.org/10.1016/j.ccell.2025.04.014/). Furthermore, the development of post-gastrulation amnioids as a stem cell-derived model of human extra-embryonic development provides a novel platform for studying early human development (ref: Gharibi doi.org/10.1016/j.cell.2025.04.025/). The integration of collecting systems in kidney organoids through innovative differentiation techniques further exemplifies the potential of organoid models in regenerative medicine (ref: Shi doi.org/10.1016/j.stem.2025.04.008/). Together, these studies highlight the versatility of organoid models in advancing our understanding of complex biological processes and disease mechanisms.

Stem cell therapy and regenerative medicine are rapidly evolving fields, with recent studies highlighting innovative approaches to enhance therapeutic outcomes. A phase 1/2 trial of lentiviral gene therapy for sickle cell disease demonstrated the feasibility of reduced-intensity conditioning for autologous transplantation of gene-modified hematopoietic stem cells, showing promising results in patient outcomes (ref: Grimley doi.org/10.1038/s41591-025-03662-2/). This approach may reduce the toxicities associated with traditional myeloablative conditioning regimens. Additionally, research on microbial cancer immunotherapy revealed that BCG administration reprograms hematopoietic stem and progenitor cells, enhancing myeloid-driven anti-tumor immunity (ref: Daman doi.org/10.1016/j.ccell.2025.05.002/). This finding underscores the potential of leveraging immune responses to improve cancer treatment outcomes. Furthermore, the expansion of plasmablasts producing commensal-reactive IgA antibodies was identified as a predictor for chronic graft-versus-host disease (cGVHD), emphasizing the importance of understanding immune dynamics in post-transplant settings (ref: Habenicht doi.org/10.1182/blood.2024027301/). Collectively, these studies illustrate the transformative potential of stem cell therapies in addressing complex diseases and improving patient care.