Cell Regeneration最新文献

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.

The advancement of tooth regeneration has offered revolutionary progress in the treatment of tooth defects and tooth loss, particularly in whole-tooth regeneration, pulp-dentin regeneration, and enamel regeneration. This review comprehensively analyzes the latest research progress in the biological foundations of tooth regeneration, stem cell applications, and tissue engineering technologies while discussing the prospects for clinical translation of these technologies. At present, pulp-dentin regeneration technology has entered clinical trials and demonstrated preliminary efficacy; however, the maturity and controllability of this technology require further enhancement. In situ whole-tooth regeneration has been achieved in animal models but still confronts ethical and functional challenges. Although the development of new materials has provided novel strategies for the epitaxial growth of enamel, enamel regeneration remains in its early stages. Tissue engineering technologies offer new avenues for tooth regeneration but still need to address issues such as immune rejection and long-term stability to realize the clinical application of tooth regeneration technologies.

Genetic and microbial factors influence inflammatory bowel disease (IBD), prompting our study on non-invasive biomarkers for enhanced diagnostic precision. Using the XGBoost algorithm and variable analysis and the published metadata, we developed the 10-species signature XGBoost classification model (XGB-IBD10). By using distinct species signatures and prior machine and deep learning models and employing standardization methods to ensure comparability between metagenomic and 16S sequencing data, we constructed classification models to assess the XGB-IBD10 precision and effectiveness. XGB-IBD10 achieved a notable accuracy of 0.8722 in testing samples. In addition, we generated metagenomic sequencing data from collected 181 stool samples to validate our findings, and the model reached an accuracy of 0.8066. The model's performance significantly improved when trained on high-quality data from the Chinese population. Furthermore, the microbiome-based model showed promise in predicting active IBD. Overall, this study identifies promising non-invasive biomarkers associated with IBD, which could greatly enhance diagnostic accuracy.

Effective therapies for peripheral nerve repair are still lacking despite active research in this field over the past years. The limited knowledge of biomolecules that equally promote axon regeneration and glial cell dynamics, which are critical for nerve regeneration, poses a major challenge in developing effective therapies. Here, we showed that the neurotrophic factor mesencephalic astrocyte-derived neurotrophic factor (MANF) equally promotes axon regeneration and glial cell dynamics favorable for nerve regeneration. Using adult rodent models, we showed that the endogenous expression of MANF is restricted to non-peptidergic sensory neurons. However, supplementation of exogenous MANF promoted the growth of all subtypes of adult sensory neurons. We also demonstrated that exogenous MANF promotes the proliferation and migration of adult primary Schwann Cells (SCs). Furthermore, we showed that local and repeated administration of MANF to injured nerves promotes axon regeneration in mice models. Finally, we devised a therapeutic approach by programming nerve-resident SCs to locally and continuously deliver MANF to injured nerves and showed that this approach improves axon regeneration. Overall, this work developed a therapeutic approach by harnessing the power of SCs as a local delivery system for MANF for nerve repair.

Exercise has been shown to influence gut microbiota composition, but the specific effects of different exercise modalities on microbial diversity remain unclear. Understanding these differences is essential for optimizing exercise programs to enhance both physical fitness and gut health. This study compared the gut microbiota profiles of participants undergoing moderate-intensity continuous training (MICT), high-intensity interval training (HIIT), and high-intensity functional training (HIFT) using 16S rRNA gene sequencing. Thirty-one previously untrained healthy university students were randomly assigned into MICT (n = 7), HIIT (n = 12) and HIFT (n = 12). The results revealed that distinct gut microbiome profiles in participants under different exercise modes. Notably, the alpha-diversity gradually increased from the MICT group to the HIFT group. In addition, there was a progressive shift towards a Faecalibacterium-dominated microbial type from HIIT to HIFT group compared to MICT group. Individuals in the HIFT group were identified to be enriched with Lactobacillus and Limosilactobacillus, along with reduced Actinomyces and Anaeromassilibacillus. Functionally, the KEGG pathway and enzyme analysis using PICRUST2 revealed that the HIFT group exhibited prominence in muscle function-related pathways and enzymes, specifically ko00280 (valine, leucine, and isoleucine degradation), as well as the enzyme EC: 3.4.11.14 (alanine aminopeptidase). In conclusion, these findings highlight how exercise modality influences gut microbial diversity, with HIFT promoting a more favorable microbial profile compared to traditional endurance training. Understanding these effects can help tailor exercise programs to improve both fitness and gut health.