Human CellPub Date : 2025-06-19DOI: 10.1007/s13577-025-01246-3
Qing Tang, Ying Yang, Jia'nan Sun
{"title":"EZH2 regulates tumor-associated macrophages by the KDM6A-mediated inflammatory response in HPV16-positive cervical cancer.","authors":"Qing Tang, Ying Yang, Jia'nan Sun","doi":"10.1007/s13577-025-01246-3","DOIUrl":"https://doi.org/10.1007/s13577-025-01246-3","url":null,"abstract":"<p><p>High-risk HPV subtypes impact the immune response in cervical cancer. Tumor-associated macrophages (TAMs) are well known to contribute to tumor development by regulating the immune response. This study aimed to analyze the mechanism of TAMs by the enhancer of zeste homolog 2 (EZH2) in HPV16<sup>+</sup> cervical cancer. The HPV16<sup>+</sup> cervical cancer cells, SiHa and CaSki, were treated with increasing concentrations of EZH2 inhibitor EPZ6438 (5, 10, 20, 40, 80 μM) for 24 h. The KDM6A expression is suppressed in a concentration-dependent manner when EZH2 activity is inhibited. Then, the cancer cells were transfected with pcDNA-control or pcDNA-KDM6A, and treated with the IC<sub>50</sub> of EPZ6438. The cell viability, levels of IL-6 and CXCL1, and p-Akt(s473)/Akt proteins were measured. The PMA-treated THP-1 cells were induced into M2 macrophages by IL-4 and IL-13. The M2 macrophages were cocultured with the conditioned cancer cells to observe the M2 polarization. In vivo experiments, the effects of EZH2 inhibition on tumor growth were investigated in nude mice. EZH2 inhibition suppressed the cell viability and inflammatory response by suppressing KDM6A in HPV16<sup>+</sup> cervical cancer cells. KDM6A overexpression suppressed the effects of EZH2 inhibition on cell viability and inflammatory response. EZH2 inhibition in cancer cells suppressed the M2 macrophages, and its mechanism was related to the KDM6A-mediated inflammatory response. In nude mice models, EZH2 inhibition effectively reduced tumor growth by regulating KDM6A. EZH2 regulated the KDM6A-mediated inflammatory response, thus affecting the polarization of M2 macrophages, leading to tumor growth in HPV16<sup>+</sup> cervical cancer. This study provided an insight into the immune modulation of EZH2 in HPV16<sup>+</sup> cervical cancer.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 4","pages":"119"},"PeriodicalIF":3.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human CellPub Date : 2025-06-11DOI: 10.1007/s13577-025-01245-4
Pooja Tiwary, Krishil Oswal, Ryan Varghese, Harsh Anchan
{"title":"Human metapneumovirus: a mini-review on the genetic and phylogenetic roots of a rising respiratory threat.","authors":"Pooja Tiwary, Krishil Oswal, Ryan Varghese, Harsh Anchan","doi":"10.1007/s13577-025-01245-4","DOIUrl":"https://doi.org/10.1007/s13577-025-01245-4","url":null,"abstract":"","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 4","pages":"118"},"PeriodicalIF":3.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Potential of platelet-rich plasma-derived exosomes for bone-defect repair: in vitro and in vivo study.","authors":"Xuepu Zhang, Limin Yang, Yaguang Wang, Zhaoliang Ban, Xiaohu Ma, Qiangqiang Zhang, Yue Zhang","doi":"10.1007/s13577-025-01244-5","DOIUrl":"https://doi.org/10.1007/s13577-025-01244-5","url":null,"abstract":"<p><p>Skeletal progenitor-enriched cells, also referred to as skeletal stem cell (SSC)-like cells, are multipotent progenitors that underpin advancements in bone bioengineering and regenerative therapy. Platelet-rich plasma-derived exosomes (PRP-EXOs) exhibit promising capabilities for enhancing osteogenic repair and addressing bone-defect challenges. Nonetheless, whether PRP-EXOs promote bone regeneration and repair by affecting SSC-like cells remains unclear. This study aimed to investigate the effects of PRP-EXOs on SSC-like cells and bone-defect regeneration and repair. PRP-EXOs were purified from rat-derived PRP, and SSC-like cells were obtained via collagenase digestion of femoral and tibial bone tissues. PRP-EXOs were identified by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. The effects of PRP-EXOs on cell viability, proliferation, migration, and osteogenic differentiation were also assessed. Femoral bone-defect models were constructed in rats and evaluated for bone regeneration and repair using microcomputed tomography, bone parameter analysis, and histological assessment. We successfully extracted PRP-EXOs and isolated SSC-like cells from Sprague Dawley rats. Incubation with PRP-EXOs increased cell viability, promoted cell proliferation and migration, and strengthened the osteogenic differentiation of SSC-like cells. Furthermore, PRP-EXO treatment reduced weight loss and accelerated new bone formation and repair in rats with femoral bone defects, accompanied by improvements in bone mineralization and collagen formation. The promotion of bone-defect repair by PRP-EXOs may depend on their promoting effects on the proliferation, migration, and osteogenic differentiation of SSC-like cells, suggesting that PRP-EXOs may be important in bone-defect treatment.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 4","pages":"117"},"PeriodicalIF":3.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Establishment and characterization of TK-DDCS1: a novel IDH1 mutated dedifferentiated chondrosarcoma cell line.","authors":"Krittamate Saisuwan, Piyanard Boonnate, Hiroki Goto, Rumi Nakagawa, Makoto Abe, Kaoru Hirabayashi, Yukio Fujiwara, Kazutaka Kikuta, Seiji Okada","doi":"10.1007/s13577-025-01235-6","DOIUrl":"https://doi.org/10.1007/s13577-025-01235-6","url":null,"abstract":"<p><p>Dedifferentiated chondrosarcoma (DDCS) is a rare and aggressive subtype of chondrosarcoma, characterized by the coexistence of a high-grade spindle or pleomorphic tumor that lacks a substantial cartilaginous matrix. Notably, it shows a mutant IDH1 incidence of over 80%. This study established a novel DDCS cell line with an IDH1 mutation, TK-DDCS1, derived from the right ilium of a 67-year-old Japanese female patient. TK-DDCS1 cells maintain the undifferentiated DDCS phenotype with the IDH1p.R132L mutation. The IDH1R132 mutation is known to be associated with a poor prognosis for chondrosarcoma, and the p.R132L mutation is a novel variant among the registered DDCS cell lines in the Cellosaurus database. The mutant IDH1 inhibitor, DS-1001b, inhibited the proliferation of TK-DDCS1 in a dose-dependent manner in both two-dimensional and spheroid cultures. The tumorigenicity of TK-DDCS1 was demonstrated through xenografting into EGFP-transgenic BALB/c Rag2-/-/Jak3-/- (EGFP-BRJ) mice, where the tumors exhibited undifferentiated phenotypes of DDCS in both morphological and immunohistochemical features. Thus, TK-DDCS1 serves as a valuable model for investigating the characteristics of DDCS and exploring molecular targeted therapies.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 4","pages":"116"},"PeriodicalIF":3.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human CellPub Date : 2025-06-02DOI: 10.1007/s13577-025-01225-8
Yixiu Long, Xuan Pei, Hongyu Liu, Xueyan Ouyang, Wei Jiang, Huijuan Yang
{"title":"Establishment and comparison of three sublines from a human uterine carcinosarcoma cell line, ESCA.","authors":"Yixiu Long, Xuan Pei, Hongyu Liu, Xueyan Ouyang, Wei Jiang, Huijuan Yang","doi":"10.1007/s13577-025-01225-8","DOIUrl":"10.1007/s13577-025-01225-8","url":null,"abstract":"<p><p>The pathogenesis of uterine carcinosarcoma (UCS) remains unclear due to a few mature cell lines. Herein, we established a new cell line, ESCA, from a Chinese woman. Especially, three sublines, named ESCA-2, ESCA-3, ESCA-5, were isolated based on the rate of cells' different sedimentation. All ESCA cells have been subcultured for more than 60 generations. ESCA sublines display different cell morphology and growth characteristics, as well as have different sensitivity to chemotherapeutic drugs. ESCA was most sensitive to paclitaxel and carboplatin, while ESCA-2 was most sensitive to ifosfamide. Besides, ESCA showed severe chromosome karyotype abnormalities and abnormal number of chromosomes. Whole exome sequence showed ESCA and its sublines, as well as tissue block shared similar single nucleotide variants, such as TP53, TRRAP mutations, while relatively large differences in mutational signature abundance. When all ESCA cells were xenotransplanted subcutaneously into BALB/c-nu mice, they developed into tumors that resembled the original tumor with positive AE1/3 and Vimentin in immunohistochemical staining. Interestingly, the transplanted tumor from ESCA-5 proliferated fastest with a relatively low level of glucose uptake evaluated by micro-PET/CT scanning. Taken together, ESCA and its sublines may be valuable tools to explore the molecular mechanism of UCS.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 4","pages":"115"},"PeriodicalIF":3.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human CellPub Date : 2025-05-30DOI: 10.1007/s13577-025-01232-9
Hongyu Lian, Miao Yu, Qi Li, Jiayi Xiao, Xin Tang, Bin Zhang, Dongxue Liu, Yongliang Xu, Mo Dong, Zitao Li, Lihong Yao, Caijuan Li
{"title":"Hypoxic breast cancer cell-derived exosomal miR-143-3p targets RICTOR to regulate M2 macrophage polarization, thereby modulating cancer cell invasiveness.","authors":"Hongyu Lian, Miao Yu, Qi Li, Jiayi Xiao, Xin Tang, Bin Zhang, Dongxue Liu, Yongliang Xu, Mo Dong, Zitao Li, Lihong Yao, Caijuan Li","doi":"10.1007/s13577-025-01232-9","DOIUrl":"https://doi.org/10.1007/s13577-025-01232-9","url":null,"abstract":"<p><p>Hypoxia is a critical mechanism within the microenvironment of tumors. Exosomes, serve as conduits for intercellular communication and transport the biomolecule miRNA by facilitating intercellular signal exchange, which partially regulate cancer metastasis. Our research investigated whether the role of hypoxic breast cancer cell-derived exosomal miR-143-3p in cancer progression. Real-time PCR explored miR-143-3p expression in hypoxia breast cancer cell-derived exosomes. Co-culturing of breast cancer with hypoxia exosome-primed M0 macrophages, transwell detected the invasiveness of breast cancer cells. Western blot showed the effect of hypoxia exosomes on the levels of M2 makers in macrophages and the epithelial-mesenchymal transition (EMT) indicators in breast cancer cells. Bioinformatics prediction and dual luciferase reporter assay determined the interaction between miR-143-3p and RICTOR. We found that exosomal miR-143-3p expression was downregulated in hypoxic conditions. Hypoxia breast cancer cell-derived exosomal miR-143-3p negatively correlated with the presentation of the M2 macrophage marker CD206 and regulated the levels of Arg-1, CD206 and CD163 mRNA levels. In addition, hypoxia exosome-mediated polarization of M2 macrophages promotes breast cancer cell migration and invasion. Mechanistically, miR-143-3p acted antagonistically with RICTOR, thereby suppressing macrophage M2 polarization. In summary, our study reveals that the hypoxia downregulates the exosomal miR-143-3p derived from breast cancer cells to increase macrophage RICTOR expression, thereby promoting M2 macrophage polarization to enhance breast cancer cell invasiveness, suggesting that miR-143-3p may be a candidate molecule for microRNA alternative therapy in breast cancer.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 4","pages":"114"},"PeriodicalIF":3.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human CellPub Date : 2025-05-29DOI: 10.1007/s13577-025-01239-2
Jian Li, Xin Su, Xiao Xu, Youbao Ye, Cailiu Wang, Ang Liu, Changchun Zhao, Wenxiu Liu, Liwen Yang, Tao Wang, Xiangyong Hao
{"title":"Biological functions and molecular mechanisms of circHIPK3 in digestive system tumors.","authors":"Jian Li, Xin Su, Xiao Xu, Youbao Ye, Cailiu Wang, Ang Liu, Changchun Zhao, Wenxiu Liu, Liwen Yang, Tao Wang, Xiangyong Hao","doi":"10.1007/s13577-025-01239-2","DOIUrl":"https://doi.org/10.1007/s13577-025-01239-2","url":null,"abstract":"<p><p>Digestive system tumors are the most common tumors worldwide with high mortality rates. Circular homeodomain-interacting protein kinase 3 (circHIPK3) is a highly abundant and stable circular RNA and have garnered significant attention in the field of cancer research. This review systematically explores potential of circHIPK3 as a clinical biomarker, clinical significance in pharmacotherapy, and molecular mechanisms that regulate biological functions such as cell proliferation, survival, migration, invasion, epithelial-mesenchymal transition, metabolism and angiogenesis in digestive system tumors. Moreover, this review further explored the influence of circHIPK3 on key signaling pathways and the potential clinical value as a diagnostic biomarker and therapeutic target. By delving into the biological functions and molecular mechanisms of circHIPK3, this review aims to provide novel research directions and theoretical guidance for the identification of new therapeutic targets and the development of individualized treatment protocols for digestive system tumors.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 4","pages":"113"},"PeriodicalIF":3.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"KS-NailMel-1: a novel cell line of nail apparatus melanoma.","authors":"Takamichi Ito, Yuka Tanaka, Keiko Tanegashima, Kiichiro Nishio, Hiroki Hashimoto, Toshio Ichiki, Fumitaka Ohno, Yumiko Kaku-Ito, Takeshi Nakahara","doi":"10.1007/s13577-025-01242-7","DOIUrl":"10.1007/s13577-025-01242-7","url":null,"abstract":"<p><p>Nail apparatus melanoma (NAM) is a specific type of cutaneous melanoma that develops in the nail apparatus of the hands and feet. The prognosis for metastatic NAM is poor due to a lack of fully effective systemic therapies. However, the difficulty in obtaining a NAM model has hindered basic research aimed at discovering effective treatment strategies. In this study, we established a NAM cell line, named KS-NailMel-1, from a primary tumor located on the nail apparatus of the left ring finger of a 68-year-old Japanese female. The cells were successfully maintained for over 9 months, exhibiting a doubling time of 38.6 ± 1.94 h. KS-NailMel-1 displayed consistent growth, spheroid formation, and invasiveness, and was confirmed to be identical to the original tumor through short tandem repeat analyses, whole-exome sequencing, and immunohistochemistry. Western blotting of the cells demonstrated the protein expression of NECTIN4, which has recently attracted attention as a potential therapeutic target for melanoma. The KS-NailMel-1 cell line represents a valuable resource for basic and preclinical research on NAM, deepening our understanding of the tumor characteristics and facilitating the development of treatment strategies for this rare form of cancer.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 4","pages":"112"},"PeriodicalIF":3.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mesenchymal stem/stromal cells-derived exosomes: possible therapeutic mechanism in inflammatory bowel disease.","authors":"Zekun Li, Luyun Liu, Yuhui Sun, Xinjuan Liu, Ping Zhang, Yue Wang, Gang Ding","doi":"10.1007/s13577-025-01243-6","DOIUrl":"https://doi.org/10.1007/s13577-025-01243-6","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract caused by dysfunction of the immune system in genetically susceptible individuals. As current pharmacologic and surgical treatments remain suboptimal, increasing attention has been directed toward exosomes derived from mesenchymal stem/stromal cells (MSCs) as alternative therapeutic approaches. MSCs are multipotent stromal cells that can be isolated from various human tissues such as bone marrow, adipose, umbilical cord and periodontal ligament. Exosomes are cell-derived membrane-bound vesicles enclosing RNAs, proteins, growth factors, and cytokines. Previous studies indicate that the anti-inflammatory, immunomodulatory, and regenerative effects of MSCs are largely mediated by MSC-derived exosomes (MSC-Exos). Therefore, this review outlines current insights into the molecular mechanisms of MSC-Exos in IBD treatment to support the future development of MSC-Exos as a therapeutic strategy, thus providing novel observations into the clinical applications of MSC-Exos in IBD management.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 4","pages":"111"},"PeriodicalIF":3.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144162792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Single-cell dynamic RNA and glycosylation sequencing reveals the mechanism underlying the differentiation of pluripotent stem cells into hematopoietic stem cells.","authors":"Wanyi Feng, Sheng Zeng, Donghui Liu, Wei Gong, Junjie Hu, Weihua Xu, Zhichao Ma, Shengmiao Fu, Xinping Chen","doi":"10.1007/s13577-025-01234-7","DOIUrl":"10.1007/s13577-025-01234-7","url":null,"abstract":"<p><p>Studying the mechanism of hematopoietic stem cells' generation from induced pluripotent stem cells in vitro can be useful for understanding embryonic hematopoiesis, as well as for the application of related cell therapy. This study aimed to delineate the process of the differentiation of induced pluripotent stem cells into hematopoietic stem cells' models and provide a theoretical basis and clinical value for the production of hematopoietic stem cells in vitro. We analyzed the differentiation model by single-cell dynamic transcriptome and glycosylation sequencing, which was divided into three differentiation stages based on the new-to-total RNA ratio and glycosylation level. Two differentiation fates were found in the pseudo-time, including hematopoietic development and other tissue development. Precursor hematopoietic cells with a high glycosylation level greatly expressed hematopoietic regulation and vascular endothelial genes, suggesting that glycosylation is associated with angiogenesis and hematopoietic regulation. The multiple differentiation events in the in vitro model are similar to those in hematopoietic development in vivo, including yolk sac hematopoiesis, cellular communication between non-potential hematopoietic subsets and potential hematopoietic subsets, gene expression, and temporal deviations in hematopoietic fate. Our study has revealed the similar hematopoiesis process in the differentiation model via single-cell dynamic RNA and glycosylation sequencing, which provides an important theoretical basis for the study of hematopoietic stem cell development.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 4","pages":"110"},"PeriodicalIF":3.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144162961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}