{"title":"Advances in research and current challenges in the treatment of advanced HER2-low breast cancer.","authors":"Qiang Qin","doi":"10.3389/fcell.2025.1451471","DOIUrl":"10.3389/fcell.2025.1451471","url":null,"abstract":"<p><p>Human epidermal growth factor receptor 2 (HER2)-low breast cancer is defined as breast cancer with an immunohistochemistry (IHC) score of 1+ or 2+ and <i>in situ</i> hybridisation (ISH)-negative. The traditional HER2 classification (negative or positive) has limitations, with only 15%-20% of the breast cancer population being positive and suitable for HER2-targeted therapy. The new clinical study, DESTINY-Breast04, shows that trastuzumab deruxtecan (T-DXd) has a significant effect on advanced HER2-low breast cancers, a classification that accounts for approximately half of the advanced breast cancer population. However, the detection methods and evaluation criteria for HER2-low breast cancer have not yet been standardised, and the toxicity and resistance mechanisms associated with T-DXd therapy are still unclear. This article focuses on these issues and describes the progress and challenges of T-DXd-related therapy in the treatment of advanced breast cancer patients with low HER2 expression.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1451471"},"PeriodicalIF":4.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771634","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}
Stella Angeli, Constantina Neophytou, Maria Kalli, Triantafyllos Stylianopoulos, Fotios Mpekris
{"title":"The mechanopathology of the tumor microenvironment: detection techniques, molecular mechanisms and therapeutic opportunities.","authors":"Stella Angeli, Constantina Neophytou, Maria Kalli, Triantafyllos Stylianopoulos, Fotios Mpekris","doi":"10.3389/fcell.2025.1564626","DOIUrl":"10.3389/fcell.2025.1564626","url":null,"abstract":"<p><p>The mechanical properties of the tumor microenvironment (TME) undergo significant changes during tumor growth, primarily driven by alterations in extracellular (ECM) stiffness and tumor viscoelasticity. These mechanical changes not only promote tumor progression but also hinder therapeutic efficacy by impairing drug delivery and activating mechanotransduction pathways that regulate crucial cellular processes such as migration, proliferation, and resistance to therapy. In this review, we examine the mechanisms through which tumor cells sense and transmit mechanical signals to maintain homeostasis in the biomechanically altered TME. We explore current computational modelling strategies for mechanotransduction pathways, highlighting the need for developing models that incorporate additional components of the mechanosignaling machinery. Furthermore, we review available methods for measuring the mechanical properties of tumors in clinical settings and strategies aiming at restoring the TME and blocking deregulated mechanotransduction pathways. Finally, we propose that proper characterization and a deeper understanding of the mechanical landscape of the TME, both at the tissue and cellular levels, are essential for developing therapeutic strategies that account for the influence of mechanical forces on treatment efficacy.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1564626"},"PeriodicalIF":4.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763153","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}
Byron Zhao, Jinsook Suh, Yan Zhang, Eric Yin, Chiho Kadota-Watanabe, In Won Chang, Jun Yaung, Isabelle Lao-Ngo, Nathan M Young, Reuben H Kim, Ophir D Klein, Christine Hong
{"title":"p75 neurotrophin receptor regulates craniofacial growth and morphology in postnatal development.","authors":"Byron Zhao, Jinsook Suh, Yan Zhang, Eric Yin, Chiho Kadota-Watanabe, In Won Chang, Jun Yaung, Isabelle Lao-Ngo, Nathan M Young, Reuben H Kim, Ophir D Klein, Christine Hong","doi":"10.3389/fcell.2025.1569533","DOIUrl":"10.3389/fcell.2025.1569533","url":null,"abstract":"<p><p>Craniofacial abnormalities are among the most prevalent congenital defects, significantly affecting appearance, function, and quality of life. While the role of genetic mutations in craniofacial malformations is recognized, the underlying molecular mechanisms remain poorly understood. In this study, we investigate the role of p75 neurotrophin receptor (p75<sup>NTR</sup>) in craniofacial development by comparing wild-type (p75<sup>NTR+/+</sup>) mice against p75<sup>NTR</sup>-deficient (p75<sup>NTR-/-</sup>) knockout mice. We employed histology, micro-CT surface distance, volumetric analysis, and geometric morphometric analysis to assess craniofacial development and growth. On postnatal day 7 (P7), p75<sup>NTR-/-</sup> mice exhibited reduced skull length compared to wild-type controls. By P28, micro-CT analysis revealed significant reductions in calvarial bone volume and trabecular bone thickness in p75<sup>NTR-/-</sup> mice. Geometric morphometric analysis identified significant shape alterations in the nasal, parietal, and occipital regions, with p75<sup>NTR-/-</sup> mice showing a shortened cranium and tapered nasal bone morphology. These findings highlight the critical role of p75<sup>NTR</sup> in regulating postnatal craniofacial development. Disruption of p75<sup>NTR</sup> signaling impairs both the growth and morphological integrity of craniofacial structures, which may contribute to the pathogenesis of congenital craniofacial abnormalities. In the future, a better understanding of the molecular mechanisms through which p75<sup>NTR</sup> mediates craniofacial development may offer valuable insights for future targeted therapeutic strategies for craniofacial defects.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1569533"},"PeriodicalIF":4.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763149","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}
Shuai Ai, Zhou Xie, Ningdao Li, Runhan Zhao, Xiao Qu, Haining Zhou, Dagang Tang, Jun Zhang, Xiaoji Luo
{"title":"Bibliometric and visualized analysis of the applications of exosomes for bone regeneration.","authors":"Shuai Ai, Zhou Xie, Ningdao Li, Runhan Zhao, Xiao Qu, Haining Zhou, Dagang Tang, Jun Zhang, Xiaoji Luo","doi":"10.3389/fcell.2025.1552727","DOIUrl":"10.3389/fcell.2025.1552727","url":null,"abstract":"<p><strong>Background: </strong>Bone defect, a common orthopedic condition, is characterized by a lengthy and impactful treatment period, posing a considerable challenge in clinical settings. Medical technology has advanced notably, and has effectively treated an increasing number of patients with bone defects. Consequently, there has been an explosion of research articles on bone regeneration, including a substantial number on the application of exosomes. Exosomes, especially those derived from stem cells, have been confirmed to be effective in bone regeneration and have garnered widespread attention in the last decade. Therefore, this study conducted a bibliometric analysis on publications related to the application of exosomes for bone regeneration. The objectives are to explore the development history and research hotspots in this field over the past 10 years, predict future development trends, and provide guidance for subsequent research.</p><p><strong>Methods: </strong>The Web of Science Core Collection (WoSCC) database was searched for articles related to exosomes and bone regeneration published from 1 January 2014, to 31 December 2023. The collected literature was analyzed using software such as Microsoft Excel, CiteSpace 6.3R1, VOSviewer 1.6.20, and the bibliometric online platform (https://bibliometric.com).</p><p><strong>Results: </strong>A total of 3,004 articles published by 2,729 institutions from 68 countries were included in this study. The number of articles on the application of exosomes for bone regeneration has increased annually over the last decade. China was the most prolific country in this field, with a total of 1,468 papers; Shanghai Jiao Tong University (China) was the institution with the highest number of publications (117 publications). In terms of authors, Xin Wang, Yi Zhang, and Yang Wang were the three who published the highest number of papers, with 14 papers each. Co-citation analysis revealed that the article published by Valadi H in 2007 has the highest number of co-citations (270 times of quotation). Additionally, most research hotspots focused on the function of exosomes and the mechanism of action. Furthermore, the importance of osteoblast differentiation and angiogenesis in bone regeneration has also garnered significant attention from scholars in this field.</p><p><strong>Conclusion: </strong>This study reviewed the research achievements on the application of exosomes for bone regeneration over the past 10 years, utilizing bibliometric analysis tools. It visualized the countries, institutions, authors, and journals that have made significant contributions to this field, revealed current research hotspots, and finally explored future development trends.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1552727"},"PeriodicalIF":4.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751880","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}
Fernanda Loureiro Almeida O'Sullivan, Ani V Das, Patricia Rojas-Ríos
{"title":"Editorial: Functional implications of Piwi proteins and piRNAs in stem cell maintenance and development.","authors":"Fernanda Loureiro Almeida O'Sullivan, Ani V Das, Patricia Rojas-Ríos","doi":"10.3389/fcell.2025.1583955","DOIUrl":"10.3389/fcell.2025.1583955","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1583955"},"PeriodicalIF":4.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751886","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}
Albina Jablonka-Shariff, Curtis Broberg, Alison K Snyder-Warwick
{"title":"Absence of T-box transcription factor 21 limits neuromuscular junction recovery after nerve injury in <i>T-bet</i>-knockout mice.","authors":"Albina Jablonka-Shariff, Curtis Broberg, Alison K Snyder-Warwick","doi":"10.3389/fcell.2025.1535323","DOIUrl":"10.3389/fcell.2025.1535323","url":null,"abstract":"<p><strong>Introduction: </strong>Terminal Schwann cells (tSCs), at the neuromuscular junction (NMJ), play critical roles in the repair of motor axon terminals at muscle, and rebuild neuronal signaling following nerve injury. Knowledge of mediators impacting tSCs post-nerve injury and in disease may guide beneficial therapies to improve motor outcomes. We previously found T-box transcription factor 21 (TBX21/TBET), classically associated with T-helper1 cells and immune cell recruitment, is expressed in tSCs at the mouse NMJ. The purpose of this study was to examine effects of <i>Tbx21</i> absence during NMJ regeneration following peripheral nerve injury.</p><p><strong>Methods: </strong>Wildtype (WT) and <i>Tbet-knockout</i> (<i>Tbet-KO</i>) mice underwent sciatic nerve transection and immediate repair. Functional muscle recovery assessment was performed with muscle force testing on mice at 2-, 3-, 4-, and 6-week (wks) and 6 months after nerve injury repair. Morphometric analyses of NMJ reinnervation, tSC number, and tSC processes were evaluated. Full NMJ reinnervation was defined as ≥75% coverage of endplates by axons. A minimum of three mice were evaluated in each group, and 50-100 NMJs were evaluated per mouse.</p><p><strong>Results: </strong><i>Tbet-KO</i> mice had significantly diminished muscle function compared to WT mice at every time point beyond 3 weeks. <i>Tbet-KO</i> mice showed just over half of the muscle force generated by WT mice at 4 weeks and 6 weeks post-injury and repair. By 6 months, <i>Tbet-KO</i> mice generated only 84.1% the muscle force of WT mice. <i>Tbet-KO</i> mice showed significantly decreased levels of fully reinnervated NMJs compared to WT mice at each time point tested. <i>Tbet-KO</i> mice also showed a lower number of tSCs with reduced cytoplasmic processes beyond NMJ area and lower number of immune cells during process of NMJ regeneration.</p><p><strong>Discussion: </strong>Our findings show that the <i>Tbx21</i> transcription factor promotes NMJ reinnervation to regain muscle function following nerve injury.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1535323"},"PeriodicalIF":4.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751915","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":"Epigenetic mechanisms in stem cell therapies for achilles tendinopathy.","authors":"Zheyang Yuan, Zheyu Yao, Xufeng Mao, Xiang Gao, Sengyi Wu, Haijiao Mao","doi":"10.3389/fcell.2025.1516250","DOIUrl":"10.3389/fcell.2025.1516250","url":null,"abstract":"<p><p>Achilles tendinopathy (AT) is a chronic degenerative tendinopathy that affects people's daily lives. Multiple clinical studies have found that current conservative treatments fail to promote quality tendon healing. Recent studies have found that stem cell therapy can target pathophysiological changes in the tendon by replenishing tendon-derived cells, promoting extracellular matrix (ECM) remodeling, and modulating the inflammatory response to improve the microenvironment of Achilles tendon regeneration. And epigenetic modifications play an important role in stem cell fate determination and function. In this review, we provided a brief overview of the biological properties of relevant stem cells. The influence of epigenetic modifications on stem cell proliferation, differentiation, and immune regulatory function in the treatment of AT was also explored. We focused on gene regulatory mechanisms controlled by DNA methylation, histones and non-coding RNAs including microRNAs, circRNAs and long non-coding RNAs. We also discuss the current challenges faced by stem cell therapies in treating AT and their potential solutions. Further research in this area will provide a more comprehensive epigenetic explanation for stem cell therapy for AT, leading to the development of stable, safe and effective stem cell therapies.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1516250"},"PeriodicalIF":4.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779404","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}
Klaudia Radoszkiewicz, Aleksandra Bzinkowska, Monika Sypecka, Dorota Sulejczak, Daniela Ferrari, Maurizio Gelati, Angelo Luigi Vescovi, Anna Sarnowska
{"title":"Unraveling the impact of human cerebrospinal fluid on human neural stem cell fate.","authors":"Klaudia Radoszkiewicz, Aleksandra Bzinkowska, Monika Sypecka, Dorota Sulejczak, Daniela Ferrari, Maurizio Gelati, Angelo Luigi Vescovi, Anna Sarnowska","doi":"10.3389/fcell.2025.1527557","DOIUrl":"10.3389/fcell.2025.1527557","url":null,"abstract":"<p><p>Human neural stem/progenitor cells (hNSCs) can potentially treat neurological diseases, but their low survival and proliferation rates after transplantation remain challenging. In our study, we preincubated hNSCs with the human cerebrospinal fluid (CSF) to obtain closer to the physiological brain environment and to assess NSC fate and their therapeutic abilities <i>in vitro</i>, <i>ex vivo</i>, and <i>in vivo</i>. We observed significant changes in the differentiation, migratory, and secretory potential of CSF-treated hNSCs, as well as their elevated neuroprotective potential after co-culture with ischemically damaged by oxygen-glucose deprivation (OGD) organotypic rat hippocampal slices culture (OHC) in comparison to the cells cultured in the standard conditions. Next, we investigated their survival and anti-inflammatory abilities in an <i>in vivo</i> ouabain-induced stroke model. This study highlighted and confirmed the critical importance of nutritional supplementation in maintaining NSC culture and enhancing its therapeutic properties.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1527557"},"PeriodicalIF":4.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751837","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":"LncRNAs in oncogenic microenvironment: from threat to therapy.","authors":"Dipanjan Roy, Bireswar Bhattacharya, Rudra Chakravarti, Prabhjot Singh, Mansi Arya, Anirban Kundu, Ajay Patil, Bhukiya Siva, Sunny Mehta, Tawsif Ahmed Kazi, Dipanjan Ghosh","doi":"10.3389/fcell.2024.1423279","DOIUrl":"10.3389/fcell.2024.1423279","url":null,"abstract":"<p><p>LncRNAs are RNA molecules of more than 200 nucleotides in length and participate in cellular metabolism and cellular responses through their diverse interactomedespite having no protein-coding capabilities. Such significant interactions also implicate the presence of lncRNAs in complex pathobiological pathways of various diseases, affecting cellular survival by modulating autophagy, inflammation and apoptosis. Proliferating cells harbour a complex microenvironment that mainly stimulate growth-specific activities such as DNA replication, repair, and protein synthesis. They also recognise damages at the macromolecular level, preventing them from reaching the next-generation. LncRNAs have shown significant association with the events occurring towards proliferation, regulating key events in dividing cells, and dysregulation of lncRNA transcriptome affects normal cellular life-cycle, promoting the development of cancer. Furthermore, lncRNAs also demonstrated an association with cancer growth and progression by regulating key pathways governing cell growth, epithelial-mesenchymal transition and metastasis. This makes lncRNAs an attractive target for the treatment of cancer and can also be used as a marker for the diagnosis and prognosis of diseases due to their differential expression in diseased samples. This review delves into the correlation of the lncRNA transcriptome with the fundamental cellular signalling and how this crosstalk shapes the complexity of the oncogenic microhabitat.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1423279"},"PeriodicalIF":4.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771621","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}