Cell Regeneration最新文献

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.

Aging is characterized by progressive functional decline driven by stem cell exhaustion, chronic inflammation, and cellular senescence. Mesenchymal progenitor cells (MPCs), which play a central role in tissue repair, are particularly vulnerable to age-associated dysfunction. Lei et al. (Cell 188:1-22, 2025) address this limitation by engineering human embryonic stem cell-derived MPCs with enhanced FOXO3 activity (termed SRCs). Intravenous administration of FOXO3-SRCs to aged cynomolgus macaques significantly slowed aging across multiple organs compared to wild-type MPCs. SRC treatment improved cognitive performance, preserved brain structure, protected bone integrity, and rejuvenated immune function. Transcriptomic and DNA methylation aging clocks revealed substantial reductions in biological age, with the most pronounced rejuvenation observed in the reproductive system, skin, lung, muscle, and hippocampus. These effects were partly attributed to SRC-derived exosomes enriched in gero-protective proteins and metabolites. Importantly, SRCs exhibited robust safety, showing no tumorigenicity or immunogenicity. This work positions FOXO3-enhanced MPCs and their exosomes as promising candidates for systemic anti-aging interventions, shifting the therapeutic paradigm from treating individual diseases to targeting the aging process itself.

Hair pigmentation is regulated by melanocyte stem cells (MeSCs) within the hair follicle. Mitochondrial dysfunction is associated with hair depigmentation, primarily due to defects in melanogenesis. However, the mechanisms by which mitochondria support MeSCs during hair pigmentation remain obscure. In this study, we investigated the role of mitochondrial deoxyguanosine kinase (DGUOK), which provides guanosine and adenosine nucleotides for mitochondrial DNA (mtDNA) replication, in hair pigmentation and MeSCs maintenance. Dguok depleted and conditional knockout mice exhibit premature hair greying. This phenotype was not due to impaired melanin production by melanocytes but was associated with a significant loss of MeSCs and mature melanocytes. Notably, Dguok deficiency decreased the expression of 13 mtDNA-encoded genes, increased the levels of reactive oxygen species (ROS) and apoptosis in MeSCs. Treatment with N-acetylcysteine (NAC), an ROS inhibitor, effectively mitigated the depigmentation and rejuvenated the MeSCs population. These findings underscore the critical role of DGUOK in regulating mtDNA integrity, which is vital for sustaining MeSCs and ensuring hair pigmentation, providing valuable insights that may inform therapeutic strategies for combating hair greying.

Deer antlers are the only mammalian organs that periodically regenerate from permanent bony protuberances (pedicles). Antler regeneration relies on the presence of pedicle periosteum (PP) and starts from regenerative healing of wounds created following the hard antler casting. Interestingly, PP deletion (removal of local factors) abolishes antler regeneration and the transition to velvet skin (shiny and hair sparsely populated) but cannot inhibit regenerative wound healing although the healed tissue is of pedicle type (scalp-like); this indicates that systemic factors from circulating blood contribute to the generic regenerative wound healing. Subsequently, we created full-thickness excisional (FTE) skin wounds on the forehead region in sika deer. Different healing outcomes ensued, namely regeneration or formation of a scar, depending on whether the intervention took place during the period of antler regeneration (ARP; spring-summer) or in the period where antler regeneration does not occur (non-ARP; winter). Forehead wounds during ARP exhibited regenerative healing, whereas during the non-ARP, healing took place but with a scar. Therefore, systemic factors from the circulating blood during the ARP must be responsible for this outcome. Topical application of deer blood plasma (a source of systemic factors) from ARP to FTE wounds in rats promoted regenerative healing, whereas, that from non-ARP failed to do so. Further evaluation showed that regenerative healing was achieved through increased cell proliferation, impaired inflammatory response, reduced myofibroblast transformation, and orchestrated collagen remodeling accompanied by an increase in the ratio of TGF-β3 to TGF-β1. Comparative proteomics analysis of deer plasma identified some highly up-regulated factors from the plasma in ARP (ARPP) with regeneration-stimulating-potential, such as IGF1 and PRG4. Topical application of IGF1 or IGF1 + PRG4 to rat FTE wounds greatly promoted regenerative healing; particularly in the combination of IGF1 and PRG4 group. In summary, our findings convincingly demonstrate that the systemic factors from deer blood taken during ARP contain factors capable of inducing regenerative wound healing and that this effect is not species-specific. Because there are almost no restrictions on the supply of deer blood in ARP, our findings have laid the foundation for devising effective therapies for scar-less wound healing in the clinical setting.