Craniosynostosis is a congenital craniofacial disorder where premature fusion of cranial sutures causes elevated intracranial pressure and neurological deficits. In this issue of Cell Stem Cell, Ma et al. demonstrate that replenishing skull progenitor cells alleviates intracranial pressure elevations in craniosynostosis by restoring the meningeal lymphatic system, improving neurocognitive function

Immune attack by natural killer (NK) cells is a major hurdle for allogeneic off-the-shelf cell therapy, especially when HLA molecules are removed. Gravina et al.1 utilized a membrane-anchored single-chain antibody (scFv) as a synthetic receptor, named “synthetic immune checkpoint engager,” to prevent attack from NK cells and macrophages.

Regenerating the lungs’ architecture after injury requires rebuilding its fibroelastic extracellular matrix scaffold. Konkimalla et al. establish that regenerative cell states (RCSs) of both epithelial and mesenchymal origin are functionally linked and indispensable for this process. Experimental ablation of RCSs causes organ degeneration, whereas their induction causes organ fibrosis.

Engineered hematopoietic stem cells can be shielded from targeted immunotherapy. Recently published in Nature, Casirati et al. utilized single-base editing of epitopes implicated in acute myeloid leukemia and healthy hematopoiesis to alter their antibody and chimeric antigen receptor (CAR) T recognition while preserving their ligand binding and enzymatic function.

Hematopoietic stem cells (HSCs), which govern the production of all blood lineages, transition through a series of functional states characterized by expansion during fetal development, functional quiescence in adulthood, and decline upon aging. We describe central features of HSC regulation during ontogeny to contextualize how adaptive responses over the life of the organism ultimately form the basis

Studies of mammalian development have advanced our understanding of the genetic, epigenetic, and cellular processes that orchestrate embryogenesis and have uncovered new insights into the unique aspects of human embryogenesis. Recent studies have now produced the first epigenetic maps of early human embryogenesis, stimulating new ideas about epigenetic reprogramming, cell fate control, and the potential

Mutation accumulation in stem cells has been associated with cancer risk. However, the presence of numerous mutant clones in healthy tissues has raised the question of what limits cancer initiation. Here, we review recent developments in characterizing mutation accumulation in healthy tissues and compare mutation rates in stem cells during development and adult life with corresponding cancer risk.

In this issue of Cell Stem Cell, Kawakami et al. develop a SARS-CoV-2 infection-competent, progenitor-derived, human vascular organoid model and uncover a role for complement factor D (CFD) in mediating microvascular immunothrombosis. This model may be applied to conditions where microvascular disease plays a major pathogenic role.

In this issue of Cell Stem Cell, Bershteyn et al.1 developed a human interneuron cell therapy that reduced spontaneous seizure activity in a mouse model of mesial temporal lobe epilepsy (MTLE). The data presented here support an ongoing phase 1/2 clinical trial for the treatment of pharmaco-resistant epilepsy in patients.

Embryo models are potentially highly impactful for human health research because their development recapitulates otherwise inaccessible events in a poorly understood area of biology, the first few weeks of human life. Casual reference to these models as “synthetic embryos” is misleading and should be approached with care and deliberation.

As China’s stem cell industry continues to develop, increasing disputes concerning stem cell-based interventions have been brought before the courts. Nonetheless, there is variability in the courts’ understanding and attitude toward the regulatory attributes of these interventions, which to some extent has multifaceted impacts on the stem cell field.

Abstract not available

Mammals favor healing with scaring over functional tissue regeneration.1 In this issue of Cell Stem Cell, Mack et al. use “super-healer” mice to identify cis-regulatory variations that direct regenerative versus fibrotic gene expression in wound fibroblasts and they uncover complement factor H as a molecular driver of skin regeneration.2

Studying human embryo development, most particularly around the time of implantation, is a challenge, yet it is necessary to improve assisted reproduction techniques. In this issue, Yu et al.1 and Karvas et al.2 improve integrated stem cell models, called blastoids, to model the peri-implantation human embryo.

Stem cell therapy uses transplantation of exogenous stem cells to repair damaged tissues. In this issue of Cell Stem Cell, Ma et al. and Herriges et al. reported durable engraftment of pluripotent stem cell (PSC)-derived airway and alveolar epithelial progenitor cells, respectively, in the mouse lung.

Abstract not available

Chemical reprogramming offers an unprecedented opportunity to control somatic cell fate and generate desired cell types including pluripotent stem cells for applications in biomedicine in a precise, flexible, and controllable manner. Recent success in the chemical reprogramming of human somatic cells by activating a regeneration-like program provides an alternative way of producing stem cells for clinical

In this issue of Cell Stem Cell, Yoo et al.1 report that replacing Trem2 knockout microglia with Trem2 wild-type microglia-like cells derived from systemically transplanted hematopoietic cells rectifies microglial dysfunction in a mouse model of amyloidosis. These findings highlight the potential of microglia replacement therapy for Alzheimer’s disease treatment.

In this issue, Jiang and colleagues employ multiple lineage-tracing approaches to elaborate on the role of Tff2+ transit-amplifying progenitor cells in the pancreatic acinar compartment of mice. This work provides insights into the steady-state homeostasis and tumor-suppressive features of certain progenitor cells and presents findings on acinar cell heterogeneity.

Exploring the early stages of human embryonic development poses significant difficulties owing to ethical and technical limitations. Two recent studies in Nature report the self-organization of human stem cells into 3D embryoids that model features of the early post-implantation stages of human development.1,2

Sixteen years after regulating advanced therapy medicinal products (ATMPs) in the European Union, few ATMPs have gained marketing authorization. Additionally, market withdrawals for commercial reasons and a lack of reimbursement are de facto blocking patient access. Here, we pinpoint the major factors underlying this roadblock and how to circumvent it.

Kidney organoids have enabled modeling of human development and disease. While methods of generating the nephron lineage are well established, new protocols to induce another lineage, the ureteric bud/collecting duct, have been reported in the past 5 years. Many reports have described modeling of various hereditary kidney diseases, with polycystic kidney disease serving as the archetypal disease, by

In this issue, Lazaro et al.1 use iPSC-derived presomitic mesoderm cells to analyze the oscillatory expression of somitic clock genes. Comparison of a wide range of species, including mouse, rabbit, cattle, rhinoceros, human, and marmoset, demonstrates an excellent correlation between biochemical reaction speed and the tempo of the clock.

It remains challenging to create a physiologically relevant human-brain-like environment that would support maturation of human pluripotent stem cell (hPSC)-derived microglia (hMGs). Schafer et al.1 (Cell, 2023) now develop an in vivo neuroimmune organoid model with mature homeostatic hMGs for the study of brain development and disease.

By developing in vitro 3D culture systems and identifying morphological and molecular events of early organogenesis, two recent studies1,2 reported exciting research advances in non-human primate embryo development.

In 2013, Japan established a conditional approval pathway for cell and gene therapies. Our analysis of the four products approved via this pathway identifies evidence suggesting shortcomings in safety and efficacy data submitted by the sponsors and raises concerns about whether this pathway is delivering on its promise.

Human pluripotent stem cells can be used to derive in vitro models recapitulating post-implantation human embryos. While useful for research purposes, such integrated embryo models raise ethical issues that need to be addressed to facilitate ethically appropriate policies and regulations that permit scientific ingenuity and medical progress.