Age-related macular degeneration (AMD) is a major cause of vision loss worldwide. The disease is caused by deterioration of the retinal pigment epithelium (RPE), a tissue that plays critical roles in the support of the photoreceptors. Cell therapies to replace damaged RPE in the non-exudative form of AMD have been under development for several decades. We review the progress of cell therapy to date and highlight some promising future directions for research in this area.

The genetic integrity of pluripotent stem cells (PSC) is critical to their applications in research and therapy, but it is compromised by frequent development of structural chromosome variants associated with malignancy. Many PSC lines exhibit remarkable genetic stability, but little is known about the basis of the known variation in genomic integrity among different PSC isolates. Here, we identify aneuploidies using RNA-seq and proteomics data from a panel of mouse embryonic stem cell (mESC) lines derived from 170 Diversity Outbred mice. We found 62 lines with detectable aneuploid subpopulations and a subset of originally XX lines that lost one chromosome X (XO). Strikingly, a much lower proportion of XX lines were aneuploid, compared to XY or XO lines. Two single-cell RNA-seq datasets demonstrated that aneuploid XY DO mESC also show lower chromosome X gene expression, and a prospective study confirmed that XY mESC accumulate higher aneuploid proportions in culture than isogenic XX lines. We identify potential mechanisms for this protective effect of X chromosome dosage, including our findings that the lines with two active X chromosomes have a higher proportion of 2-cell-like cells and higher expression of X-linked tumor suppressor genes, both features associated with the maintenance of genomic integrity, and that they compete more robustly in co-culture with chromosomally abnormal cells than XY cells.

Stem cell-based embryo models provide innovative ways to explore the principles of human development but also pose new challenges for regulation. Recent guidelines have argued for case-by-case evaluation of stem cell-based embryo model research but it is still unclear what exactly such oversight should consider. Here we argue that effective review requires the identification of a set of attributes by which to evaluate research proposals. To define these, the underlying ethical values and morally relevant biological features present in embryo models must be identified to enable the practical implementation of oversight. We propose that developmental stage, tissue/organ integrity, fetal potential and the capacity to form neural circuits should be used together for evaluation purposes. We also highlight the importance of the wider context, including the proposed uses of embryo models, public perception and individual researcher responsibilities, and thus provide a general framework for regulatory consideration of human embryo model research.

The International Society for Stem Cell Research (ISSCR) document “Standards For Human Stem Cell Use in Research” put forward a checklist for scientific journals to use in the assessment of compliance with its reporting standards. A trial implementation of this checklist at Stem Cell Reports revealed consistent gaps in the reporting of critical data relating to the cells and experimental methodologies employed in published manuscripts.

Two international stem cell consortia, the International Stem Cell Initiative (ISCI) and the International Stem Cell Biobanking Initiative (ISCBI, www.iscbi.org ) held a workshop on June 15th 2025 in Hong Kong on genetic variants in human pluripotent stem cell (hPSC) lines and accurate and standardized documentation of donor/hPSC genetic information including ethnicity. The occurrence and detection of genetic variants is a key issue for assuring reproducible stem cell research data and the safety of stem cell derived medicinal products. Presentations by leading experts addressed the nature of hPSC genetic variants, their detection and accurate recording of genetic data and ethnicity. The audience of stem cell researchers, cell banking directors and experts in ethic, policy and stem cell databases, from 13 countries across the globe, discussed progression of the ISCI consortium’s efforts in providing further data and thought leadership on the management of genetic variants, and the challenges for standardizing biobanking approaches for hPSC genetic data including ethnicity. This paper records the key elements of this discussion and the conclusions and consensus reached and ongoing work to provide guidance for hPSC biobanks.

Human pluripotent cell lines that cannot generate cortical organoids are rescued by an epigenetic reboot.

Advancing the use of human stem cell-based models on preclinical and regulatory testing fields requires the performance of rigorous and reproducible research. Quality standards and reporting best practices should be promoted to ensure the reliability and translatability of stem cell models and results. Strategies to increase awareness and implementation of best practices and standards will require training initiatives and collaboration across relevant stakeholders. Overall, improving the quality and reproducibility of stem cell-based models and methods through best practices and standards will accelerate their adoption in industrial and regulatory contexts and ultimately drive the development of effective therapies and safer chemicals.

Pluripotency, the capacity to generate all cells of the body, is a defining property of a transient population of epiblast cells found in pre-, peri- and post-implantation mammalian embryos. As development progresses, the epiblast cells undergo dynamic transitions in pluripotency states, concurrent with the specification of extra-embryonic and embryonic lineages. Recently, stem cell-based models of pre- and post-implantation human embryonic development have been developed using stem cells that capture key properties of the epiblast at different developmental stages. Here, we review early primate development, comparing pluripotency states of the epiblast in vivo with cultured pluripotent cells representative of these states. We consider how the pluripotency status of the starting cells influences the development of human embryo models and, in turn, what we can learn about the human pluripotent epiblast. Finally, we discuss the limitations of these models and questions arising from the pioneering studies in this emerging field.

Today, human pluripotent stem cell technologies find widespread application across biomedical research, as models for early human development, as platforms for functional human genomics, as tools for the study of disease, drug screening and toxicology, and as a renewable source of cellular therapeutics for a range of intractable diseases. The foundations of this human pluripotent stem cell revolution rest on advances in a wide range of disciplines, including cancer biology, assisted reproduction, cell culture and organoid technology, somatic cell nuclear transfer, primate embryology, single-cell biology, and gene editing. This review surveys the slow emergence of the study of human pluripotency and the exponential growth of the field during the past several decades.

The power and scope of disease modeling can be markedly enhanced through the incorporation of broad genetic diversity. The introduction of pathogenic mutations into a single inbred mouse strain sometimes fails to mimic human disease. We describe a cross-species precision disease modeling platform that exploits mouse genetic diversity to bridge cell-based modeling with whole organism analysis. We developed a universal protocol that permitted robust and reproducible neural differentiation of genetically diverse human and mouse pluripotent stem cell lines and then carried out a proof-of-concept study of the neurodevelopmental gene DYRK1A . Results in vitro reliably predicted the effects of genetic background on Dyrk1a loss-of-function phenotypes in vivo. Transcriptomic comparison of responsive and unresponsive strains identified molecular pathways conferring sensitivity or resilience to Dyrk1a1A loss and highlighted differential messenger RNA isoform usage as an important determinant of response. This cross-species strategy provides a powerful tool in the functional analysis of candidate disease variants identified through human genetic studies.

Comparative studies that integrate genetically diverse mouse models and in vitro cell-based assays will accelerate drug discovery for precision medicine.

Stem cells exist in vitro in a spectrum of interconvertible pluripotent states. Analyzing hundreds of hiPSCs derived from different individuals, we show the proportions of these pluripotent states vary considerably across lines. We discover 13 gene network modules (GNMs) and 13 regulatory network modules (RNMs), which are highly correlated with each other suggesting that the coordinated co-accessibility of regulatory elements in the RNMs likely underlie the coordinated expression of genes in the GNMs. Epigenetic analyses reveal that regulatory networks underlying self-renewal and pluripotency are more complex than previously realized. Genetic analyses identify thousands of regulatory variants that overlapped predicted transcription factor binding sites and are associated with chromatin accessibility in the hiPSCs. We show that the master regulator of pluripotency, the NANOG-OCT4 Complex, and its associated network are significantly enriched for regulatory variants with large effects, suggesting that they play a role in the varying cellular proportions of pluripotency states between hiPSCs. Our work bins tens of thousands of regulatory elements in hiPSCs into discrete regulatory networks, shows that pluripotency and self-renewal processes have a surprising level of regulatory complexity, and suggests that genetic factors may contribute to cell state transitions in human iPSC lines.

Wildlife biodiversity is essential for healthy, resilient and sustainable ecosystems. For biologists, this diversity also represents a treasure trove of genetic, molecular and developmental mechanisms that deepen our understanding of the origins and rules of life. However, the rapid decline in biodiversity reported recently foreshadows a potentially catastrophic collapse of many important ecosystems and the associated irreversible loss of many forms of life on our planet. Immediate action by conservationists of all stripes is required to avert this disaster. In this Spotlight, we draw together insights and proposals discussed at a recent workshop hosted by Revive & Restore, which gathered experts to discuss how stem cell technologies can support traditional conservation techniques and help protect animal biodiversity. We discuss reprogramming, in vitro gametogenesis, disease modelling and embryo modelling, and we highlight the prospects for leveraging stem cell technologies beyond mammalian species.

Abstract Introduction The efficacy of perioperative bundled interventions implemented at a multicenter level has been poorly studied. Methods A colorectal 6-element prevention bundle (antibiotic prophylaxis, oral antibiotic prophylaxis (OAP), mechanical bowel preparation (MBP), laparoscopy, normothermia, and wound retractor), introduced in 61 hospitals, was analysed. Surgical site infection (SSI) rates were compared before (G1, 2011–2016), and after (G2, 2016–2020) the bundle implementation. Results 37849 procedures were included. 5462 overall SSI (14.43%), and 2838 (7.5%) organ-space SSI (O/S-SSI) were detected. SSI decreased from 18.38% to 10.62% with the application of the bundle (OR 0,503). Similarly, O/S-SSI diminished from 9.15% (G1) to 5.72% (G2), OR 0.602. Compared to the previous year, SSI decreased by 23% after the first year of bundle implementation. 29.26% of SSIs were diagnosed post-discharge. 54.5% required readmission. The reduction was similar between high, medium and low volume hospitals. Overall SSI was 16.71%, when no measure was applied, and 6.23% when all 6 were implemented. Lack of application of the bundle increased the probability of SSI (OR 3.020) and O/S-SSI (OR 1.556). In a univariate analysis, all measures except normothermia were associated with a decrease in overall SSI, while only laparoscopy and OAP were for O/S-SSI. Multivariate analysis confirmed that laparoscopy, OAP, and wound protectors decrease overall SSI, but only OAP and laparoscopy had an effect on O/S-SSI. Conclusions A preventive bundle decreased overall and O/S SSI rates in elective colon and rectal surgery. The OR for SSI was 1.5 to 3 times higher before than after the bundle implementation.

The second week of embryonic development is a critical phase of the human life cycle and one that has been largely inaccessible to scientific investigation. Recent studies of human embryo models built from stem cells promise to yield dramatic insights into the key events of cell specification and morphogenesis that occur during this brief window of embryogenesis.

A human embryo’s legal definition and its entitlement to protection vary greatly worldwide. Recently, human pluripotent stem cells have been used to form in vitro models of early embryos that have challenged legal definitions and raised questions regarding their usage. In this light, we propose a refined legal definition of an embryo, suggest “tipping points” for when human embryo models could eventually be afforded similar protection to that of embryos, and then revisit basic ethical principles that might help to draft a roadmap for the gradual, justified usage of embryo models in a manner that aims to maximize benefits to society.

In the earliest stages of mammalian development, individual cells possess the unrestricted potential to form a new organism. Researchers are closing in on the goal of growing these cells in the laboratory.

As noted elsewhere in this issue (Ludwig et al.), the International Society for Stem Cell Research (ISSCR) Standards Task Force has recently published its guidelines document, Standards for the Use of Human Stem Cells in Research. The standards document establishes a set of basic principles for best practice in our field and represents the culmination of many months of work by a group of international experts, as well as a broad external review process, dedicated to maintaining rigor and reproducibility in stem cell research across the discipline. Early in the process, the Standards Task Force realized that while producing this document was an essential exercise, some mechanism for the implementation of its recommendations would be critical if it were to have an impact on stem cell research. Therefore, the task force sought the engagement of other stakeholders beyond the research community, including funding bodies and journal editors, who would be in position to help bring the recommendations of the initiative into practice. Journal editors were enthusiastic participants in the task force exercise, and they suggested from the start that it would be very useful if the initiative could generate a simple checklist for authors to complete, one that gave editors and reviews an indication of the degree to which a manuscript met the key recommendations present in the document. To be clear, the intent of the task force was never to promulgate a set of rules that authors had follow, or to police the field. Instead, the goal was to increase clarity and transparency in the reporting of certain key quality control measures unique to the field of stem cell research. The checklist (see SnapShot in this issue), which is similar in format to editorial policy checklists already in use at many journals, will enable authors to disclose the critical experimental details of their research for review and potentially replication. As the journal of the ISSCR, we at Stem Cell Reports wish to be at the forefront of this effort to improve rigor and reproducibility. Therefore, from October 2023 forward, we will be requiring authors to complete and submit this checklist along with their original research manuscripts. For the first 6 months of this new policy, the checklist will be collected for information only, and will not be used in the review process, either at the editorial level or as a part of external peer review. The trial period will enable us to assess the overall response to the questions and to obtain feedback from authors. After the trial period, the editors and reviewers will be able to consult the checklist during review of a manuscript. However, it will be up to reviewers to determine whether the information provided by the authors is sufficient to ensure confidence in the experimental results presented. Any author responses to the checklist will be viewed in light of the particular experimental design and research findings in a manuscript and the data that support these findings. The checklist in fact makes explicit a set of standards that most of our reviewers are cognizant of and should be following already. It is our belief that the use of this checklist will help to raise awareness of key issues of research practice standards throughout the field, and we encourage all of you to read it not only before you submit the manuscript, but also before you begin a project. In most cases, the requested information will be available, and it will just be a matter of ensuring that it is properly reported. We hope that authors will provide us with their views on the checklist and the task force recommendations. We look forward to hearing from you.