Cell Regeneration最新文献

To adapt to gravitational forces during the transition to terrestrial life, animals evolved specialized paw skin to withstand their body weight and allow for locomotion. In a recent Cell article, Di et al. demonstrate SLURP1 as an endoplasmic reticulum (ER) membrane protein that protects palmoplantar keratinocytes from mechanical stress by preserving SERCA2b activity and inhibiting the pPERK-NRF2 signaling under mechanical pressure.

The adult mammalian heart lacks the capacity to regenerate after injury, leading to heart failure. While most of the research focused on the cardiomyocyte proliferation around the infarct zones, a new study (Fan et al., Cell Stem Cell 32(1563-1576):e1511, 2025) reveals a novel mechanism in the remote endocardial zone. They identified lysozyme 2 (Lyz2) as a critical regulator, where its sustained activity in the non-regenerative hearts promotes lysosomal degradation of the extracellular matrix (ECM). Then, the breakdown of ECM was found to induce cardiomyocyte apoptosis near the endocardium. Importantly, both the genetic deletion of Lyz2 or the pharmacological inhibition of lysosomal degradation activity in mice after myocardial infarction (MI) preserved the ECM, reduced cardiomyocyte apoptosis, diminished scarring, and improved cardiac function. This work highlights LYZ2 as a novel therapeutic target for promoting heart repair in humans.

Primary human hepatocytes (PHH) are used as the FDA-recognized "gold standard" for liver-related studies in vitro. The world's first PHH group standard (T/CSCB 0008-2021, CSCB standard) was released by Chinese Society for Cell Biology in 2021. In order to justify this standard, six key quality attributes of ten different batches from commercial PHHs, including cell viability, cell morphology, cell markers, albumin secretion, drug metabolism function and bile secretion, were characterized using the designated test methods in the standard. The PHHs from various batches all exhibited typical hepatocytic morphology, high cell viability, and sufficient albumin secretion; whereas, tremendous variations in cell markers, drug metabolism functions, and bile secretion were unexpectedly detected across the board. Flow cytometric assessment of hepatocyte markers revealed the percentages of ALB⁺ or HNF4A⁺cells in six batches of PHHs, ranging from 49.4% to 98.9% and from 37.7% to 91.4%, respectively. Single cell transcriptomic analysis also revealed significant cell heterogeneity across the different batches, with the proportions of hepatocytes ranging from 69.2% to 98.9%. Considerable heterogeneity in drug metabolism functions across the batches were also found in substrate clearance rate (SCR) and metabolite formation rate (MFR) for six representative CYP450 enzymes, while the results didn't influence current SCR attribute of CYP3A4. Metabolic capacity and purity are two independent attributes for PHH. The varied biliary excretion indexes around criteria (30%) indicated heterogeneity of PHH biliary excretion capacity. These results confirmed the robustness of most quality attributes in current CSCB standard, while highlighting the need to refine remaining parameters to enhance its practical applicability.

The adult mammalian heart exhibits minimal regenerative capacity due to postnatal cell-cycle arrest of cardiomyocytes. In contrast, lower vertebrates such as zebrafish retain the ability to fully regenerate heart after injury. This capacity is driven not only by transcriptional and structural plasticity but also by metabolic reprogramming that supports cardiomyocyte proliferation. Adult mammalian cardiomyocytes lack both features, remaining largely refractory to regenerative cues. These limitations have prompted efforts to identify extrinsic genetic and metabolic regulators capable of reactivating proliferative competence in adult cardiomyocytes. In this review, we highlight recent advances in the molecular and metabolic control of cardiomyocyte cell-cycle reentry, focusing on strategies that modulate dedifferentiation, proliferation, and redifferentiation as well as metabolic state transitions. We also examine emerging translational approaches in swine models, which more closely recapitulate human cardiac physiology than rodents. Together, these insights provide a roadmap for unlocking endogenous regenerative pathways and identify key challenges in translating these findings into therapies for heart failure.

Diabetes mellitus is a common and serious metabolic disease globally, characterized by increased blood glucose levels. The major pathogenesis is the functional impairment of insulin-producing beta cells in the pancreas and the lack of insulin secretion. Although both type 1 and type 2 diabetes develop through distinct pathological mechanisms, they lead to the destruction and/or dysfunction of beta cells, resulting in inadequate beta cell mass to maintain normal blood glucose levels. For this reason, therapeutic agents capable of inducing beta cell proliferation can be considered a possible approach to restore beta cell abundance and treat type 1 and type 2 diabetes. Although several methods have been found to promote the replication of beta cells in animal models or cell lines, it is still challenging to promote the effective proliferation of beta cells in humans. This review highlights the different agents and mechanisms that facilitate pancreatic beta cell regeneration. Numerous small molecules have been discovered to influence beta cell proliferation, primarily by targeting cellular pathways such as DYRK1A, adenosine kinase, SIK, and glucokinase. Additionally, receptors for TGF-β, EGF, insulin, glucagon, GLP-1, SGLT2 inhibitors, and prolactin play critical roles in this process. Stem cell-based clinical trials are also underway to assess the safety and efficacy of stem cell therapies for patients with type 1 and type 2 diabetes. We have emphasized alternative therapeutic pathways and related strategies that may be employed to promote the regeneration of pancreatic beta cells. The knowledge raised within this review may help to understand the potential drug-inducible targets for beta cell regeneration and pave the way for further investigations.

Neural regeneration stands at the forefront of neuroscience, aiming to repair and restore function to damaged neural tissues, particularly within the central nervous system (CNS), where regenerative capacity is inherently limited. However, recent breakthroughs in biotechnology, especially the revolutions in genetic engineering, materials science, multi-omics, and imaging, have promoted the development of neural regeneration. This review highlights the latest cutting-edge technologies driving progress in the field, including optogenetics, chemogenetics, three-dimensional (3D) culture models, gene editing, single-cell sequencing, and 3D imaging. Prospectively, the advancements in artificial intelligence (AI), high-throughput in vivo screening, and brain-computer interface (BCI) technologies promise to accelerate discoveries in neural regeneration further, paving the way for more precise, efficient, and personalized therapeutic strategies. The convergence of these multidisciplinary approaches holds immense potential for developing transformative treatments for neural injuries and neurological disorders, ultimately improving functional recovery.

Embryo models derived from pluripotent stem cells (PSCs) have become powerful tools for dissecting mammalian embryonic development and advancing regenerative medicine. Two recent studies in Cell and Cell Stem Cell report major advances in generating mouse embryo models that replicate development up to early organogenesis (equivalent to embryonic day 8.5~8.75). Li et al. describe a purely chemical strategy to reprogram mouse embryonic stem cells (mESCs) into induced embryo founder cells (iEFCs) capable of forming complete embryo models (iEFC-EMs). In parallel, Yilmaz et al. demonstrate transgene-free generation of post-gastrulation models (TF-SEMs) from naive mESCs and induced pluripotent stem cells (iPSCs) using a similar chemical cocktail. Both models faithfully recapitulate key developmental events, including gastrulation, neural tube formation, cardiogenesis, and somitogenesis. These advances not only deepen understanding of early mammalian development but also pave the way for applications in regenerative medicine and disease modeling.

Spinal cord injury (SCI) triggers a complex cascade of cellular and molecular responses, yet the complex cellular communication remains incompletely understood. This study explored how intercellular communication contributes to the activation of microglia and astrocytes after SCI. Here, we integrated four datasets using single-cell RNA sequencing (scRNA-seq) or single-nucleus RNA sequencing (snRNA-seq) and constructed a comprehensive cellular atlas of the injured spinal cord. Transcriptomic changes in microglia and astrocytes were analyzed. We identified CD44 as a key receptor in SPP1-mediated microglial activation, which represented a subpopulation involved in inflammatory response in microglia. We defined a gliogenesis subpopulation of astrocytes that emerged at 3 dpi, which became the predominant cell type in the injured spinal cord. These astrocytes highly expressed the Nucleolin (Ncl) gene and interacted via the Pleiotrophin (Ptn) signaling pathway, which is associated with astrocyte proliferation. To validate these findings, we utilized a crush injury model. Flow cytometry of isolated microglia and astrocytes confirmed the upregulation of CD44 in microglia and NCL in astrocytes in response to SCI. In vivo results confirmed that the CD44 positive microglia accumulated and PLA results further confirmed the combination of SPP1 with CD44. In parallel, the upregulated expression of NCL in astrocytes facilitated their proliferation, underscoring the role of the NCL receptor in gliogenesis after SCI. In vitro validation demonstrated that exogenous SPP1 upregulates CD44 expression by promoting the phosphorylation of p65 and activating the NF-κB pathways in BV2 microglia, and that high expression of IL-6 indicates the activation of inflammation. PTN may enhance NCL expression and thus facilitates astrocyte proliferation. Collectively, our study identified key receptors that regulated inflammation responses and gliogenesis. Targeting the CD44 and NCL receptors may provide promising therapeutic strategies to modulate inflammation and promote tissue repair after SCI.

In the field of reproductive medicine, delaying ovarian aging and preserving fertility in cancer patients have long been core issues and relentless pursuits. Female germline stem cells (FGSCs) have been shown to repair aging or damaged ovarian structures and to restore ovarian reproductive and endocrine function. With their unlimited proliferation and directed differentiation into oocytes, FGSCs bring new hope to patients with ovarian insufficiency, malignant tumors, and others needing fertility preservation. In this review, we introduce the role of FGSCs in ovarian fertility preservation and regenerative repair, emphasizing the regulatory pathways of FGSCs in restoring ovarian function. We discuss the unique advantages of FGSCs in infertility treatment, including fertility preservation, animal gene editing, and regenerative medicine. This article aims to offer new research insights for advancing the clinical translation of FGSCs by exploring them from multiple perspectives, such as origin, regulation, and application.