Frontiers in Cell and Developmental Biology最新文献

{"title":"Proteasome dynamics in response to metabolic changes.","authors":"Cordula Enenkel, Oliver P Ernst","doi":"10.3389/fcell.2025.1523382","DOIUrl":"10.3389/fcell.2025.1523382","url":null,"abstract":"<p><p>Proteasomes, essential protease complexes in protein homeostasis, adapt to metabolic changes through intracellular movements. As the executive arm of the ubiquitin-proteasome system, they selectively degrade poly-ubiquitinated proteins in an ATP-dependent process. The primary proteasome configuration involved in this degradation is the 26S proteasome, which is composed of a proteolytically active core particle flanked by two regulatory particles. In metabolically active cells, such as proliferating yeast and mammalian cancer cells, 26S proteasomes are predominantly nuclear and actively engaged in protein degradation. However, during nutrient deprivation or stress-induced quiescence, proteasome localization changes. In quiescent yeast, proteasomes initially accumulate at the nuclear envelope. During prolonged quiescence with decreased ATP levels, proteasomes exit the nucleus and are sequestered into cytoplasmic membraneless organelles, so-called proteasome storage granules (PSGs). In mammalian cells, starvation and stress trigger formation of membraneless organelles containing proteasomes and poly-ubiquitinated substrates. The proteasome condensates are motile, reversible, and contribute to stress resistance and improved fitness during aging. Proteasome condensation may involve liquid-liquid phase separation, a mechanism underlying the assembly of membraneless organelles.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1523382"},"PeriodicalIF":4.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating oxidative stress targeting treatments in <i>in vitro</i> models of placental stress relevant to preeclampsia.","authors":"Dinara Afrose, Matt D Johansen, Valentina Nikolic, Natasa Karadzov Orlic, Zeljko Mikovic, Milan Stefanovic, Zoran Cakic, Philip M Hansbro, Lana McClements","doi":"10.3389/fcell.2025.1539496","DOIUrl":"10.3389/fcell.2025.1539496","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia is a complex pregnancy disorder characterized by the new onset of hypertension and organ dysfunction, often leading to significant maternal and fetal morbidity and mortality. Placental dysfunction is a hallmark feature of preeclampsia, which is often caused by inappropriate trophoblast cell function in association with oxidative stress, inflammation and/or pathological hypoxia. This study explores the role of oxidative stress in trophoblast cell-based models mimicking the preeclamptic placenta and evaluates potential therapeutic strategies targeting these mechanisms.</p><p><strong>Methods: </strong>Uric acid (UA) and malondialdehyde (MDA) concentrations were measured in human plasma from women with preeclampsia (n = 24) or normotensive controls (n = 14) using colorimetric assays. Custom-made first trimester trophoblast cell line, ACH-3P, was exposed to various preeclampsia-like stimuli including hypoxia mimetic (dimethyloxalylglycine or DMOG, 1 mM), inflammation (tumour necrosis factor or TNF-α, 10 ng/mL) or mitochondria dysfunction agent, (Rhodamine-6G or Rho-6G, 1 μg/mL), ± aspirin (0.5 mM), metformin (0.5 mM), AD-01 (100 nM) or resveratrol (15 µM), for 48 h. Following treatments, UA/MDA, proliferation (MTT), wound scratch and cytometric bead, assays, were performed.</p><p><strong>Results: </strong>Overall, MDA plasma concentration was increased in the preeclampsia group compared to healthy controls (p < 0.001) whereas UA showed a trend towards an increase (p = 0.06); when adjusted for differences in gestational age at blood sampling, MDA remained (p < 0.001) whereas UA became (p = 0.03) significantly correlated with preeclampsia. Our 2D first trimester trophoblast cell-based <i>in vitro</i> model of placental stress as observed in preeclampsia, mimicked the increase in UA concentration following treatment with DMOG (p < 0.0001), TNF-α (p < 0.05) or Rho-6G (p < 0.001) whereas MDA cell concentration increased only in the presence of DMOG (p < 0.0001) or Rho-6G (p < 0.001). Metformin was able to abrogate DMOG- (p < 0.01), Rho-6G- (p < 0.0001) or TNF-α- (p < 0.01) induced increase in UA, or DMOG- (p < 0.0001) or TNF-α- (p < 0.05)induced increase in MDA. AD-01 abrogated UA or MDA increase in the presence of TNF-α (p < 0.001) or Rho-6G (p < 0.001)/DMOG (p < 0.0001), respectively. The preeclampsia-like stimuli also mimicked adverse impact on trophoblast cell proliferation, migration and inflammation, most of which were restored with either aspirin, metformin, resveratrol, or AD-01 (p < 0.05).</p><p><strong>Conclusion: </strong>Our 2D <i>in vitro</i> models recapitulate the response of the first trimester trophoblast cells to preeclampsia-like stresses, modelling inappropriate placental development, and demonstrate therapeutic potential of repurposed treatments.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1539496"},"PeriodicalIF":4.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to polystyrene nanoplastics impairs sperm metabolism and pre-implantation embryo development in mice.","authors":"Yingdong Liu, Fengdan Hao, Haixin Liang, Wenqiang Liu, Yi Guo","doi":"10.3389/fcell.2025.1562331","DOIUrl":"https://doi.org/10.3389/fcell.2025.1562331","url":null,"abstract":"<p><strong>Introduction: </strong>Microplastics and nanoplastics are prevalent environmental contaminants. Recent reports indicate that polystyrene nanoparticles may adversely impact male reproductive health. This study aims to examine the effects of polystyrene exposure on sperm metabolism and the development of pre-implantation embryos.</p><p><strong>Methods: </strong>In this study, male C57BL/6 mice were orally gavage-administered polystyrene nanoplastics (60 nm, 20 mg/kg/day) for 35 days to assess their impact on male reproduction and early embryonic development. Experiments included testicular transcriptome analysis, sperm metabolomics, sperm motility and fertilization assays, embryonic ROS detection, and RNA sequencing of 2-cell embryos, revealing the adverse effects of polystyrene exposure on sperm metabolism and embryo development.</p><p><strong>Results: </strong>The results revealed that oral gavage of polystyrene to male mice induced a pronounced immune-inflammatory response in testicular tissue, reduced sperm motility, and significantly lowered the fertilization rate. Notably, sperm from treated mice exhibited substantial metabolic disruptions, affecting key pathways, including glycerophospholipid biosynthesis and DNA repair. After fertilization, embryos at the 2-cell stage suffered damage in apoptotic and DNA repair pathways, subsequently impairing early embryo development.</p><p><strong>Discussion: </strong>In conclusion, this study demonstrated that the oral gavage administration of polystyrene nanoplastics to male mice significantly affects male reproductive function, resulting in abnormalities in early embryonic development and alterations in associated gene expression profiles. These findings offer essential scientific insights for future research into sperm-mediated transgenerational effects and their impact on early embryonic development.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1562331"},"PeriodicalIF":4.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overview of distinct 8-oxoguanine profiles of messenger RNA in normal and senescent cancer cells.","authors":"Jingwen Huang, Yu Lin, Yingying Zhao, Lingbo Wei","doi":"10.3389/fcell.2025.1443888","DOIUrl":"https://doi.org/10.3389/fcell.2025.1443888","url":null,"abstract":"<p><strong>Background: </strong>Cellular senescence plays a key role in the development of cancer, but the underlying mechanisms are unknown. Recently, several recent studies have shown that RNA methylation is closely related to cancer cell aging. 8-Oxoguanine (o⁸G) is an important and widely distributed methylation modification whose role in cancer cell senescence is far from elucidated.</p><p><strong>Methods: </strong>In this study, senescent cancer cell models (CaCO₂ cells) were constructed by knocking down the ADAR1 gene. RNA immunoprecipitation sequencing was used to identify the o⁸G peaks on messenger RNA (mRNA) of normal CaCO₂ cells and senescent CaCO₂ cells, and the distribution characteristics of mRNA o⁸G modification were identified. Further bioinformatics analysis of the sequencing data was performed to preliminarily elucidate the potential function of the o⁸G-modified mRNA.</p><p><strong>Results: </strong>There were significant differences in mRNA o⁸G modification distribution between normal and senescent CaCO₂ cells. It is suggested that o⁸G modification may play a key role in inducing cancer cells or promoting cancer cell senescence. Gene ontology (GO) enrichment analysis showed that the mRNAs modified by o⁸G were enriched in Cellular component organization or biogenesis, Focal adhesion, and RNA binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the genes modified by o⁸G are concentrated in Focal adhesion signaling pathway, Small cell lung cancer signaling pathway and Proteoglycans in cancer signaling pathway.</p><p><strong>Conclusion: </strong>This study preliminarily revealed the different distribution patterns of o⁸G modification between normal CaCO₂ cells and senescent CaCO₂ cells. Our study established the link between o⁸G modification and cancer cell senescence, which provides a new insight into the mechanism of cancer cell senescence and a potential therapeutic target for subsequent cancer treatment.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1443888"},"PeriodicalIF":4.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of the effects of <i>P4ha1</i> and <i>P4ha2</i> deletion on post-translational modifications of fibrillar collagens in mouse skin.","authors":"Vivek Sarohi","doi":"10.3389/fcell.2025.1527839","DOIUrl":"https://doi.org/10.3389/fcell.2025.1527839","url":null,"abstract":"<p><strong>Introduction: </strong>Collagens, the most abundant proteins in mammals, play pivotal roles in maintaining tissue structure, functions, cell-to-cell communication, cellular migration, cellular behavior, and growth. Structures of collagens are highly complex due to the presence of dynamic post-translational modifications (PTMs), such as hydroxylations (on prolines and lysine residues) and O-glycosylation (on hydroxylysines) enzymatically catalyzed during biosynthesis in the endoplasmic reticulum. Collagen PTMs are essential for maintaining structural stability, elasticity, and different functions of collagens. The most prevalent modification in fibrillar collagens is prolyl 4-hydroxylation catalyzed by collagen prolyl 4-hydroxylases (C-P4Hs). Prolyl 4-hydroxylation on collagens plays a critical role in collagen biosynthesis, thermostability, and cell-collagen interactions. Collagens are large proteins. Different regions of collagen perform different functions, so the presence or absence of a PTM on a particular collagen site can affect its functioning. However, comprehensive site-specific identification of these PTMs on fibrillar collagen chains of mice skin has not been performed yet. Furthermore, the effects of prolyl 4-hydroxylase alpha 1 (P4HA1) and P4HA2 on 3-hydroxyproline, 5-hydroxylysine, and O-glycosylation sites of fibrillar collagen chains have not yet been explored.</p><p><strong>Methodology: </strong>This study presents a comprehensive PTM analysis of fibrillar collagen chains extracted from the skin of different mutants of C-P4Hs (<i>P4ha1</i> ^<i>+/-</i> ; <i>P4ha2-/-</i>, <i>P4ha1</i> ^<i>+/+</i> ; <i>P4ha2-/-</i>, <i>P4ha1</i> ^<i>+/-</i> ; <i>P4ha2</i> ^<i>+/-</i> , <i>P4ha1</i> ^<i>+/+</i> ; <i>P4ha2</i> ^<i>+/-</i> ) and wild-type mice. In this study, proteomics-based comprehensive PTM site identification by MS2 level ions from raw mass spectrometry data was performed, and MS1-level quantification was performed for PTM occupancy percentage analysis.</p><p><strong>Results and discussion: </strong>A total of 421 site-specific PTMs were identified on fibrillar collagen chains (COL1A1, COL1A2, and COL3A1) extracted from wild-type mice skin. A total of 23 P4HA1-specific and seven P4HA2-specific 4-hydroxyproline sites on fibrillar collagen chains were identified. Moreover, it was found that the <i>P4ha1</i> and <i>P4ha2</i> deletion can affect the 3-hydroxyproline occupancy percentages in mice skin. Interestingly, increased levels of lysyl 5-hydroxylation were detected upon partial deletion of <i>P4ha1</i> and full deletion of <i>P4ha2</i>. These findings show that the effects of deletion of prolyl 4-hydroxylases are not limited to less 4-hydroxylation on some specific proline sites, but it can also modulate the prolyl 3-hydroxylation, lysyl 5-hydroxylation, and O-glycosylation occupancy percentages in the fibrillar collagen chains in a site-specific manner.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1527839"},"PeriodicalIF":4.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant and animal-derived fusion nanovesicles rescue inflammation-compromised osteogenic potential of periodontal ligament stem cells.","authors":"Jingxiong Lin, Manchun Li, Linglu Wang, Xingyu Lu, Quanle Xu, Hongbo Chen, Dongling Dai","doi":"10.3389/fcell.2025.1512238","DOIUrl":"10.3389/fcell.2025.1512238","url":null,"abstract":"<p><p>Periodontitis is a chronic inflammatory disease affecting the supporting tissues of the teeth and has emerged as a global public health issue. Current therapies primarily address pathogenic factors and alleviate symptoms, with limited options available for complete restoration and reconstruction of already absorbed periodontal bone tissue. In this study, we developed a nanotherapeutic strategy utilizing fusion nanovesicles (FVs) to modulate the inflammatory microenvironment and create a regenerative niche for periodontal ligament stem cells (PDLSCs), which play a crucial role in periodontal tissue repair. The FVs are composed of <i>Scutellaria baicalensis</i> nanovesicles (SBNVs) with anti-<i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>) and anti-inflammatory properties, combined with PDLSC membrane-derived nanovesicles genetically engineered to express TNFR1. These FVs preserved the biological activity of SBNVs and the immunomodulatory function of PDLSCs. Additionally, FVs effectively captured and cleared TNF-α from the microenvironment through TNFR1. Moreover, FVs alleviated the inflammatory response of PDLSCs induced by <i>P. gingivalis</i>-LPS (Pg-LPS) and TNF-α, restoring their proliferation, migration, and osteogenic differentiation capabilities. Hence, this nanotherapeutic strategy holds great potential for treating periodontitis.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1512238"},"PeriodicalIF":4.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metal-dependent cell death resistance contribute to lymph node metastasis of oral squamous cell carcinoma.","authors":"Xuan-Hao Liu, Guang-Rui Wang, Nian-Nian Zhong, Zheng-Rui Zhu, Yao Xiao, Zheng Li, Lin-Lin Bu, Bing Liu","doi":"10.3389/fcell.2025.1541582","DOIUrl":"10.3389/fcell.2025.1541582","url":null,"abstract":"<p><strong>Objectives: </strong>Ferroptosis and cuproptosis can be summarized as metal-dependent cell death. This study aimed to explore the expression of metal-dependent cell death resistance (MCDR) characteristics in tumor cells of oral squamous cell carcinoma (OSCC) and to explore its relationship with lymph node metastasis (LNM).</p><p><strong>Methods: </strong>By integrating single-cell data of OSCC from public databases, an expression matrix comprising 127,149 cells was constructed. Gene set scores were calculated using the irGSEA package, and GO and KEGG analyses were performed to identify enriched pathways. The R package monocle3 was employed to calculate the cell trajectory and infer evolutionary patterns. The MuSiC2 package was employed to enable the evaluation of cell proportions. Cell-cell interaction information was analyzed using the CellChat package. The expression of cathepsin V (CTSV), glutathione peroxidase 4 (GPX4), and cyclin-dependent kinase inhibitor 2A (CDKN2A) was validated via immunohistochemistry and multiplex immunohistochemistry in oral mucosa (OM), non-metastatic primary tumors (nPT), and metastatic primary tumors (mPT). Additionally, R package oncoPredict was utilized to identify potential drug sensitivities.</p><p><strong>Results: </strong>The malignant cells in OSCC were divided into five subtypes, among which Epi_2 existed more in mPT and had higher MCDR characteristics. In addition, Epi_2 enriched multiple malignant-related pathways such as HEDGEHOG, NOTCH, and MYC. The spatial transcriptome and bulk RNA data verified that the proportion of Epi_2 in mPT was higher than that in nPT. Cell communication analysis showed that the effect of Epi_2 on endothelial cells was enhanced, which was mainly reflected in VEGFR and CXCL signaling pathways. Immunohistochemical results showed that the expression of Epi_2 characteristic markers CTSV and GPX4 in mPT was significantly higher than that in nPT. Multiplex immunohistochemical results showed that the co-expression cells of CTSV, GPX4 and CDKN2A in mPT were more than those in nPT. OSCC patients with high Epi_2 characteristics may have immunotherapy resistance and anti-EGFR treatment resistance. Doramapimod was identified as a sensitive drug.</p><p><strong>Conclusion: </strong>There is a type of malignant cells with characteristics of MDCR in OSCC, which is related to LNM and treatment resistance. It provides a predictive marker for early diagnosis of LNM.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1541582"},"PeriodicalIF":4.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Filtered and unfiltered lipoaspirates reveal novel molecular insights and therapeutic potential for osteoarthritis treatment: a preclinical <i>in vitro</i> study.","authors":"Alissa Behn, Saskia Brendle, Marianne Ehrnsperger, Magdalena Zborilova, Thomas M Grupp, Joachim Grifka, Nicole Schäfer, Susanne Grässel","doi":"10.3389/fcell.2025.1534281","DOIUrl":"10.3389/fcell.2025.1534281","url":null,"abstract":"<p><strong>Introduction: </strong>Orthobiologics, such as autologous nanofat, are emerging as a potential treatment option for osteoarthritis (OA), a common degenerative joint causing pain and disability in the elderly. Nanofat, a minimally processed human fat graft rich in stromal vascular fraction (SVF) secretory factors, has shown promise in relieving pain. This study aimed to elucidate the molecular mechanisms underlying nanofat treatment of OA-affected cells and compare two filtration systems used for nanofat preparation.</p><p><strong>Methods: </strong>Chondrocytes and synoviocytes were isolated from articular cartilage and synovium of 22 OA-patients. Lipoaspirates from 13 OA-patients were emulsified using the Adinizer^® or Lipocube^™ Nano filter systems to generate nanofat. The fluid phase of SVF from both filtered and unfiltered lipoaspirates was applied to OA-affected cells. Luminex multiplex ELISA were performed with lipoaspirates and cell supernatants alongside functional assays evaluating cell migration, proliferation, metabolic activity, and senescence.</p><p><strong>Results: </strong>A total of 62 cytokines, chemokines, growth factors, neuropeptides, matrix-degrading enzymes, and complement components were identified in lipoaspirates. Among these, significant concentration differences were observed for TIMP-2, TGF-ß₃, and complement component C3 between the filtered and unfiltered samples. Nanofat enhanced chondrocyte proliferation and migration, as well as synoviocyte migration and metabolic activity, while reducing chondrocyte metabolic activity. Pain-related factors like β-NGF, MCP-1, Substance P, VEGF, and αCGRP were reduced, while anti-inflammatory TGF-β₁₊₃ increased and pro-inflammatory cytokines (IL-5, IL-7, IL-15, and IFN-γ) decreased. Nanofat also elevated secretion of complement components and TIMPs in both cell types. Notably, our results revealed no significant differences in cellular effects between sSVF filtered using the Adinizer^® and Lipocube^™ Nano systems, as well as compared to unfiltered sSVF.</p><p><strong>Discussion: </strong>Here, we provide first insights into how autologous nanofat therapy may ameliorate OA by enhancing chondrocyte proliferation and synoviocyte migration while modulating inflammatory and pain-related factors. However, further research is needed to determine its effects on cartilage regeneration.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1534281"},"PeriodicalIF":4.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles for the 3D genome in the cell cycle, DNA replication, and double strand break repair.","authors":"Katherine A Giles, Phillippa C Taberlay, Anthony J Cesare, Mathew J K Jones","doi":"10.3389/fcell.2025.1548946","DOIUrl":"10.3389/fcell.2025.1548946","url":null,"abstract":"<p><p>Large eukaryotic genomes are packaged into the restricted area of the nucleus to protect the genetic code and provide a dedicated environment to read, copy and repair DNA. The physical organisation of the genome into chromatin loops and self-interacting domains provides the basic structural units of genome architecture. These structural arrangements are complex, multi-layered, and highly dynamic and influence how different regions of the genome interact. The role of chromatin structures during transcription via enhancer-promoter interactions is well established. Less understood is how nuclear architecture influences the plethora of chromatin transactions during DNA replication and repair. In this review, we discuss how genome architecture is regulated during the cell cycle to influence the positioning of replication origins and the coordination of DNA double strand break repair. The role of genome architecture in these cellular processes highlights its critical involvement in preserving genome integrity and cancer prevention.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1548946"},"PeriodicalIF":4.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D connective micro-fragment enriched with stromal vascular fraction in osteoarthritis: chondroprotective evidence in a preclinical <i>in vivo</i> model.","authors":"Giovanna Desando, Matilde Tschon, Lucia Martini, Maria Sartori, Gianluca Giavaresi, Milena Fini, Antonella Cellamare, Carlo Soranzo, Cristina Longinotti, Martina D'Alessandro, Livia Roseti, Brunella Grigolo","doi":"10.3389/fcell.2025.1533405","DOIUrl":"10.3389/fcell.2025.1533405","url":null,"abstract":"<p><strong>Introduction: </strong>Adipose-derived cell therapies are one of the most common regenerative therapeutic options to alleviate the multi-component damage of osteoarthritis (OA). Adipose stromal vascular fraction (SVF) has gained scientific consensus for its ability to interact protectively with the joint microenvironment. Recently, the wide range of enzyme-free tissue processing systems has outperformed classical treatments, because of their ability to produce connective micrografts enriched with the SVF (mctSVF). This preclinical <i>in vivo</i> study evaluates the chondroprotective potential of a newly generated mctSVF compared with <i>in vitro</i> expanded adipose stromal cells (ASC) in OA.</p><p><strong>Methods: </strong>A mild grade of OA was induced through bilateral anterior cruciate ligament transection (ACLT) surgery in 32 Specific Pathogen Free (SPF) Crl: KBL (NZW) male rabbits followed by the surgical excision of inguinal adipose tissue. After 2 months, OA joints were treated with an intra-articular (IA) injection of mctSVF or ASC. Local biodistribution analysis was used to determine migration patterns of PKH26-labelled cells in the knee joint after 1 month. Efficacy was assessed by gross analysis, histology and immunohistochemistry on the osteochondral unit, synovial membrane and meniscus.</p><p><strong>Results: </strong>We elucidate the effectiveness of a one-step approach based on mechanical isolation of mctSVF. Through epifluorescence analysis, we found a similar pattern of cell distribution between cell treatments, mainly towards articular cartilage. Similar regenerative responses were observed in all experimental groups. These effects included: (i) osteochondral repair (promotion of typical anabolic markers and reduction of catabolic ones); (ii) reduction of synovial reactions (reduced synovial hypertrophy and inflammation, and change of macrophage phenotype to a more regenerative one); and (iii) reduction of degenerative changes in the meniscus (reduction of tears).</p><p><strong>Discussion: </strong>Our study demonstrates the validity of a novel mechanical system for the generation of the mctSVF micrograft with chondroprotective potential in a preclinical model of moderate OA. The resulting final product can counteract inflammatory processes beyond the OA microenvironment and protect cartilage through the colonization of its structure. The intact and active microanatomy of mctSVF makes it a suitable candidate for translational medicine to treat OA without the need for cell manipulation as with ASC.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1533405"},"PeriodicalIF":4.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}