{"title":"Intestinal organoids in inflammatory bowel disease: advances, applications, and future directions.","authors":"Jianzhen Ren, Silin Huang","doi":"10.3389/fcell.2025.1517121","DOIUrl":"https://doi.org/10.3389/fcell.2025.1517121","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD), characterized by chronic gastrointestinal inflammation, is a significant global health challenge. Traditional models often fail to accurately reflect human pathophysiology, leading to suboptimal treatments. This review provides an overview of recent advancements in intestinal organoid technology and its role in IBD research. Organoids, derived from patient-specific or pluripotent stem cells, retain the genetic, epigenetic, and structural characteristics of the native gut, allowing for precise modeling of key aspects of IBD. Innovations in CRISPR editing, organoid-microbe co-cultures, and organ-on-a-chip systems have enhanced the physiological relevance of these models, facilitating drug discovery and personalized therapy screening. However, challenges such as vascularization deficits and the need for standardized protocols remain. This review underscores the need for interdisciplinary efforts to bridge the gap between models and the complex reality of IBD. Future directions include the development of scalable vascularized models and robust regulatory frameworks to accelerate therapeutic translation. Organoids hold promise for unraveling IBD heterogeneity and transforming disease management.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1517121"},"PeriodicalIF":4.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149971","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":"Editorial: Genotoxic pathways of reproductive outcomes.","authors":"Irene Iavarone, Asok K Dasmahapatra","doi":"10.3389/fcell.2025.1614251","DOIUrl":"10.3389/fcell.2025.1614251","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1614251"},"PeriodicalIF":4.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141743","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}
Thi-Hang Tran, Donny Lukmanto, Mei Chen, Olaf Strauß, Toshiharu Yamashita, Osamu Ohneda, Shinichi Fukuda
{"title":"Characterization and neurogenic responses of primary and immortalized Müller glia.","authors":"Thi-Hang Tran, Donny Lukmanto, Mei Chen, Olaf Strauß, Toshiharu Yamashita, Osamu Ohneda, Shinichi Fukuda","doi":"10.3389/fcell.2025.1513163","DOIUrl":"10.3389/fcell.2025.1513163","url":null,"abstract":"<p><p>Primary Müller glia (MG) have been reported to exhibit a neurogenic capacity induced by small molecules. However, whether immortalized mouse MG cell lines exhibit neurogenic capacities similar to those of primary mouse MG remains unclear. In this study, we examined the morphology, proliferation rate, and marker profile of primary MG cells isolated from postnatal mouse pups with two immortalized mouse MG cell lines, QMMuC-1 and ImM10, in a standard growth medium. After chemical induction, we compared the morphology, markers, direct neuronal reprogramming efficiency, and axon length of these cell types in two culture media: Neurobasal and DMEM/F12. Our results showed that in standard growth medium, QMMuC-1 and ImM10 cells displayed similar morphology and marker profiles as primary MG cells, with the only differences observed in nestin expression. However, QMMuC-1 and ImM10 cells exhibited much higher proliferation rates than the primary MG cells. Following chemical treatment in both Neurobasal and DMEM/F12 media, a subset of primary MG, QMMuC-1, and ImM10 cells was induced to differentiate into immature neuron-like cells by day 7. While primary MG cells showed similar neuronal reprogramming efficiency and axon length extension in both media, QMMuC-1 and ImM10 cells displayed variations between the two culture media. Moreover, some of the induced neuronal cells derived from primary MG cells expressed HuC/D and Calbindin markers, whereas none of the cells derived from QMMuC-1 and ImM10 cells expressed these markers. Subsequent observations revealed that induced immature neuron-like cells derived from primary MG cells in both types of media and those derived from ImM10 cells cultured in DMEM/F12 survived until day 14. Taken together, our findings suggest that the two immortalized cell lines, QMMuC-1 and ImM10, exhibited neurogenic capacities similar to those of primary MG cells to some extent but did not fully recapitulate all their characteristics. Therefore, careful consideration should be given to culture conditions and the validation of key results when using immortalized cells as a substitute for primary MG cells.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1513163"},"PeriodicalIF":4.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141658","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":"Biological disturbance of MiR-425 and its application prospects in cardiovascular diseases.","authors":"Shan Zhou, Bo Han","doi":"10.3389/fcell.2025.1593241","DOIUrl":"10.3389/fcell.2025.1593241","url":null,"abstract":"<p><p>MiR-425 is a biological molecule that has potential applications in cardiovascular diseases. It can regulate biological functions by combining with LncRNAs, binding with proteins, and changing the differentiation of immune cells. MiR-425 also has a role as a biomarker of disease. In cardiovascular diseases, it has clinical significance in reducing inflammation and heart repair, inducing angiogenesis, improving the prediction of atherosclerosis, reducing cardiac fibrosis, and regulating atrial natriuretic peptide to affect cardiovascular function. Target gene prediction and KEGG enrichment analysis are also mentioned.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1593241"},"PeriodicalIF":4.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141654","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":"Mechanisms of the FLASH effect: current insights and advances.","authors":"Giulia Rosini, Esther Ciarrocchi, Beatrice D'Orsi","doi":"10.3389/fcell.2025.1575678","DOIUrl":"10.3389/fcell.2025.1575678","url":null,"abstract":"<p><p>Radiotherapy is a fundamental tool in cancer treatment, utilized in over 60% of cancer patients during their treatment course. While conventional radiotherapy is effective, it has limitations, including prolonged treatment durations, which extend patient discomfort, and toxicity to surrounding healthy tissues. FLASH radiotherapy (FLASH-RT), an innovative approach using ultra-high-dose-rate irradiation, has shown potential in selectively sparing normal tissues while maintaining unaltered tumor control. However, the precise mechanisms underlying this \"FLASH effect\" remain unclear. This mini-review explores key hypotheses, including oxygen depletion, radical-radical interactions, mitochondrial preservation, differential DNA damage repair, and immune modulation. Oxygen levels significantly affect tissue response to radiation by promoting radical recombination, preserving mitochondrial function, and differentially activating DNA repair pathways in normal versus tumor tissues. However, the extent to which oxygen depletion contributes to the FLASH effect remains debated. Additionally, FLASH-RT may modulate the immune response, reducing inflammation and preserving immune cell function. To further enhance its therapeutic potential, FLASH-RT is increasingly being combined with complementary strategies such as radioprotectors, immunomodulators, and nanotechnology platforms. These combinations aim to amplify tumor control while further reducing normal tissue toxicity, potentially overcoming current limitations. Despite promising preclinical evidence, the exact mechanisms and clinical applicability of FLASH-RT require further investigation. Addressing these gaps is crucial for optimizing FLASH-RT and translating its potential into improved therapeutic outcomes for cancer patients. Continued research is essential to harness the full benefits of the FLASH effect, offering a paradigm shift in radiation oncology.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1575678"},"PeriodicalIF":4.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141778","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}
Chao Ma, Jianbin Chang, Olivia S Hazelwood, M Arif Ashraf, Qiong Nan
{"title":"Establishing cell polarity in plants: the role of cytoskeletal structures and regulatory pathways.","authors":"Chao Ma, Jianbin Chang, Olivia S Hazelwood, M Arif Ashraf, Qiong Nan","doi":"10.3389/fcell.2025.1602463","DOIUrl":"10.3389/fcell.2025.1602463","url":null,"abstract":"<p><p>Cell polarity is a fundamental mechanism of plant cells that drives cellular specialization and the formation of diverse cell types. It regulates critical developmental events, including polarized tip growth (such as pollen tubes and root hairs), epidermal patterning (such as trichome branching and asymmetric cell division in stomata). The establishment and maintenance of cell polarity rely on the cytoskeleton-mediated polarized distribution of specific proteins and organelles. In particular, cell-type-specific actin and microtubule dynamic structures are pivotal for maintaining polarity. For example, actin cables and short actin fragments are critical for pollen tube growth, while actin clusters and microtubule rings are involved in trichome branching, and actin patches contribute to stomatal mother cell polarization. Beyond directing the polarization of organelles and proteins, the cytoskeleton itself serves as an intrinsic cue for polarity. For instance, actin patches in stomatal precursor cells act as self-organizing polarity landmarks. Despite the diversity of cytoskeletal structures and their functions, common regulators, such as Rop GTPase signaling pathways, WAVE/SCAR complexes, and motor proteins regulate the assembly and function of these structures. Recent advances have revealed new regulatory mechanisms, such as microtubule exclusion zones guiding asymmetric divisions during Arabidopsis stomatal development, and the role of actin rings in regulating xylem pit formation. These discoveries contribute to a deeper understanding of the cytoskeleton's crucial role in polarity regulation. In this review, we highlight the key cytoskeletal structures involved in the establishment of cell polarity in plants and discuss the molecular mechanisms underlying their spatiotemporal assembly. We also address emerging questions regarding the cytoskeleton's role in cell polarity and development.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1602463"},"PeriodicalIF":4.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141775","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}
Margarita Matiukhova, Anastasia Ryapolova, Vladimir Andriianov, Vasiliy Reshetnikov, Sophia Zhuravleva, Roman Ivanov, Alexander Karabelsky, Ekaterina Minskaia
{"title":"A comprehensive analysis of induced pluripotent stem cell (iPSC) production and applications.","authors":"Margarita Matiukhova, Anastasia Ryapolova, Vladimir Andriianov, Vasiliy Reshetnikov, Sophia Zhuravleva, Roman Ivanov, Alexander Karabelsky, Ekaterina Minskaia","doi":"10.3389/fcell.2025.1593207","DOIUrl":"10.3389/fcell.2025.1593207","url":null,"abstract":"<p><p>The ability to reprogram mature, differentiated cells into induced pluripotent stem cells (iPSCs) using exogenous pluripotency factors opened up unprecedented opportunities for their application in biomedicine. iPSCs are already successfully used in cell and regenerative therapy, as various drug discovery platforms and for <i>in vitro</i> disease modeling. However, even though already 20 years have passed since their discovery, the production of iPSC-based therapies is still associated with a number of hurdles due to low reprogramming efficiency, the complexity of accurate characterization of the resulting colonies, and the concerns associated with the safety of this approach. However, significant progress in many areas of molecular biology facilitated the production, characterization, and thorough assessment of the safety profile of iPSCs. The number of iPSC-based studies has been steadily increasing in recent years, leading to the accumulation of significant knowledge in this area. In this review, we aimed to provide a comprehensive analysis of methods used for reprogramming and subsequent characterization of iPSCs, discussed barriers towards achieving these goals, and various approaches to improve the efficiency of reprogramming of different cell populations. In addition, we focused on the analysis of iPSC application in preclinical and clinical studies. The accumulated breadth of data helps to draw conclusions about the future of this technology in biomedicine.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1593207"},"PeriodicalIF":4.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127058","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}
Abdulrahman Johor, A S M Mahadiuzzaman, Abdulaziz Abdullah Alqusayer, Saleh Abdulaziz Alkarim, F A Dain Md Opo
{"title":"<i>In vivo</i> and <i>in vitro</i> therapeutic evaluation of bone marrow-derived mesenchymal stem cells in liver cancer treatment.","authors":"Abdulrahman Johor, A S M Mahadiuzzaman, Abdulaziz Abdullah Alqusayer, Saleh Abdulaziz Alkarim, F A Dain Md Opo","doi":"10.3389/fcell.2025.1521809","DOIUrl":"10.3389/fcell.2025.1521809","url":null,"abstract":"<p><p>Hepatocellular carcinoma is the seventh most common kind of cancer worldwide and the second largest cause of cancer-related deaths in males, behind lung cancer. Globally, 866,000 people were diagnosed with hepatocellular carcinoma (HCC) in 2022, and nearly 42,240 new cases will be identified in 2025 in the United States. Using stem cells obtained from bone marrow can effectively reduce the number of malignant tumor cells through the induction of an epigenetic impact. We obtained bone marrow-derived mesenchymal stem cells (BM-MSCs) from mice and collected the conditioned medium (CM) from cultured cells with 90% confluency. The effect of the CM was identified using both 2D and 3D sphere cultures of wild-type human liver cancer cell line (HepG2), considering variations in sphere size and percentage. A cell death study was conducted using the cell cytotoxicity (MTT) kit, while the quantity of stem cells was determined by immunohistochemistry and gene expression analysis. The effectiveness of our therapy was demonstrated by an <i>in vivo</i> assessment of BM-MSCs through intravenous injection and the currently available anticancer drug cisplatin. <i>In vitro</i>, the combination treatment resulted in a synergetic effect, leading to 74% cell death in both adherent and spherical cultures when treated with 25 µM of cisplatin and 90%CM. <i>In vivo</i>, the histological study indicated a decrease in tumor size and number following treatment with cisplatin and BM-MSCs. The study lasted 18 weeks and revealed that the body weight of mice improved across all treatment groups, with the combination group exhibiting the most significant improvement. Both <i>in vitro</i> and <i>in vivo</i> studies showed the synergetic effect of cisplatin and isolated conditioned medium. Our study aimed to identify more efficient therapeutic approaches utilizing stem cells and existing marketed medications to minimize adverse effects with better efficacy.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1521809"},"PeriodicalIF":4.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127057","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}
Amro M Soliman, Mohamed Soliman, Syed Sajid Hussain Shah, Habeeb Ali Baig, Nawal Salama Gouda, Bandar Theyab Alenezi, Awwad Alenezy, Ahmed M S Hegazy, Muhammad Jan, Elhassan Hussein Eltom
{"title":"Molecular dynamics of inflammation resolution: therapeutic implications.","authors":"Amro M Soliman, Mohamed Soliman, Syed Sajid Hussain Shah, Habeeb Ali Baig, Nawal Salama Gouda, Bandar Theyab Alenezi, Awwad Alenezy, Ahmed M S Hegazy, Muhammad Jan, Elhassan Hussein Eltom","doi":"10.3389/fcell.2025.1600149","DOIUrl":"10.3389/fcell.2025.1600149","url":null,"abstract":"<p><p>Inflammation is a critical part of innate immune response that is essential for exclusion of harmful stimuli and restoration of tissue homeostasis. Nonetheless, failure to resolve inflammation results in chronic inflammatory conditions, including autoimmune diseases. Conventionally, resolution of inflammation was deemed a passive process; however, evidence indicates that it entails active, highly regulated molecular and cellular events involving efferocytosis-driven macrophage reprogramming, post-transcriptional regulatory mechanisms and the production of specialized pro-resolving mediators (SPMs). These processes collectively restore tissue homeostasis and prevent chronic inflammation. Emerging therapeutic approaches targeting these pathways demonstrate promising results in preclinical studies and clinical trials, enhancing resolution and improving overall disease outcome. This resulted in a paradigm shift from conventional anti-inflammatory strategies to resolution-focused treatment. Yet, challenges remain due to the complexity of resolution mechanisms and tissue-specific differences. This review summarizes current advances in inflammation resolution, emphasizing emerging concepts of resolution pharmacology. By employing endogenous mechanisms facilitating resolution, novel therapeutic applications can effectively manage several chronic inflammatory disorders.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1600149"},"PeriodicalIF":4.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127086","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}
Yongqiang Chen, Saeid Ghavami, Paul C Park, Joy Irobi
{"title":"Editorial: Decoding cell fate: the critical roles of extracellular vesicles.","authors":"Yongqiang Chen, Saeid Ghavami, Paul C Park, Joy Irobi","doi":"10.3389/fcell.2025.1615951","DOIUrl":"10.3389/fcell.2025.1615951","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1615951"},"PeriodicalIF":4.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127059","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}