{"title":"Establishment of a novel benign meningioma cell line spontaneously immortalized under hypoxic conditions.","authors":"Takaaki Ishikawa, Masahide Matsuda, Hiroshi Ishikawa, Junko Toyomura, Akihiro Ohyama, Noriaki Sakamoto, Alexander Zaboronok, Eiichi Ishikawa","doi":"10.1007/s13577-024-01151-1","DOIUrl":"10.1007/s13577-024-01151-1","url":null,"abstract":"<p><p>Meningiomas are the most frequent brain tumors, typically benign and curable by surgery. However, some patients experience repeated recurrences from residual tumors. To address such cases, the development of novel therapeutic options is crucial. For this purpose, the availability of cell lines that possess the characteristics of benign meningiomas is essential. Here, we established a benign meningioma cell line under 3% O<sub>2</sub> hypoxic conditions without the induction of immortalization genes. This cell line, named TKB-MEN2, has been stably grown for over two years with more than 20 passages. There were no hotspot telomerase reverse transcriptase (TERT) promoter mutations or cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) homozygous deletions, which are genetic features typical of malignant meningiomas. Cultured under hypoxic conditions, this cell line showed fewer characteristics of cellular senescence, such as morphological changes, IL-6 secretion, and lower senescence-associated b-galactosidase activity, compared to the same cell line cultured under 20% O<sub>2</sub> conditions. This immortalized non-transgenic cell line appears to reflect the characteristics of a genuine benign meningioma, potentially allowing the identification of new therapeutic targets and the development of novel therapies for benign meningiomas.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 1","pages":"22"},"PeriodicalIF":3.4,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752083","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 : 2024-11-28DOI: 10.1007/s13577-024-01154-y
Juncun Yao, Li Sun, Feng Gao, Wei Zhu
{"title":"Mesenchymal stem/stromal cells: dedicator to maintain tumor homeostasis.","authors":"Juncun Yao, Li Sun, Feng Gao, Wei Zhu","doi":"10.1007/s13577-024-01154-y","DOIUrl":"10.1007/s13577-024-01154-y","url":null,"abstract":"<p><p>Mesenchymal stem/stromal cells (MSCs) act as a factor in tumor recurrence after drug treatment with their involvement observed in various cancer types. As a constituent of the tumor microenvironment (TME), MSCs not only provide support to tumor growth but also establish connections with diverse cell populations within the TME, serving as mediators linking different tumor-associated components. MSCs play an important role in maintaining tumor progression due to their stem cell properties and remarkable differentiation capacity. Given the intensification of tumor research and the encouraging results achieved in recent years,the aim of this article is to investigate the supportive role of MSCs in tumor cells as well as in various cellular and non-cellular components of the tumor microenvironment. Furthermore, the article shows that MSCs do not have a specific anatomical ecological niche and describes the contribution of MSCs to the maintenance of tumor homeostasis on the basis of homing, plasticity and tumor-forming properties. By elucidating the critical roles of different components of TME, this study provides a comprehensive understanding of tumor therapy and may offer new insights into defeating cancer.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 1","pages":"21"},"PeriodicalIF":3.4,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741091","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 NCC-GCTB14-C1 and NCC-GCTB15-C1: two novel patient-derived cell lines of giant cell tumor of bone.","authors":"Shuhei Iwata, Takuya Ono, Rei Noguchi, Julia Osaki, Yuki Adachi, Yomogi Shiota, Shintaro Iwata, Shogo Nishino, Akihiko Yoshida, Seiji Ohtori, Akira Kawai, Tadashi Kondo","doi":"10.1007/s13577-024-01150-2","DOIUrl":"10.1007/s13577-024-01150-2","url":null,"abstract":"<p><p>Giant cell tumor of bone (GCTB) is a rare bone tumor that is genetically characterized by a unique mutation in the H3-3A gene. Curative surgical resection is the standard treatment. Unfortunately, a considerable proportion of patients with GCTB have local recurrence and pulmonary metastasis after surgical treatment, and current chemotherapy treatments have shown non-effective. Considering the heterogeneity of the disease, patient-derived cancer models established from multiple cases are required. Therefore, we aimed to establish novel GCTB cell lines for use in preclinical studies. In this study, we successfully established two GCTB cell lines, NCC-GCTB14-C1 and NCC-GCTB15-C1. Both cell lines retained the genetic characteristics of the original tumors, constantly proliferated, and exhibited migratory activity. These cells formed spheroids with morphologically variable phenotypes. We found that they were compatible with chemosensitivity assays, and drug screening using these cell lines led to the identification of potential therapeutic candidates for GCTB. Therefore, NCC-GCTB14-C1 and NCC-GCTB15-C1 may be useful for elucidating the pathogenesis of and developing novel treatments for GCTB.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 1","pages":"20"},"PeriodicalIF":3.4,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741088","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":"In Vitro differentiation of hair-follicle bulge stem cells into synaptophysin-expressing neurons: a potential new approach for neuro-regeneration.","authors":"Mohamad Mahjoor, Maliheh Nobakht, Fatemehsadat Ataei Kachouei, Hamidreza Zalpoor, Fatemeh Heidari, Abazar Yari, Sanaz Joulai Veijouye, Hojjatollah Nazari, Nayereh Sajedi","doi":"10.1007/s13577-024-01146-y","DOIUrl":"10.1007/s13577-024-01146-y","url":null,"abstract":"<p><p>Stem cells, particularly bulge hair follicle stem cells (HFSCs), have recently attracted significant interest due to their potential for tissue repair and regeneration. These cells, marked by their expression of Nestin (a neural stem cell marker), suggest the possibility of neural differentiation into neurons. This study investigated the use of retinoic acid (RA) and epidermal growth factor (EGF) to induce HFSC transformation into mature neurons, identified by synaptophysin expression. Rat whisker follicles were cultured in a medium suitable for HFSC survival and proliferation. Immunostaining techniques were used to identify HFSCs and assess their differentiation into neural cells. The addition of RA and EGF to the culture medium aimed to induce this differentiation. Findings demonstrate that HFSCs expressed Nestin, indicating their pluripotent nature. Treatment with RA and EGF resulted in synaptophysin expression, a marker of mature neurons, which was absent in the control group. However, this treatment group also displayed a decrease in the expression of other neural markers (βIII tubulin and NeuN). This study suggests that a combination of RA and EGF can accelerate HFSC differentiation into synaptophysin-positive cells in vitro. This research paves the way for further exploration of its potential application in neuro-regeneration.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 1","pages":"19"},"PeriodicalIF":3.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640089","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 : 2024-11-13DOI: 10.1007/s13577-024-01147-x
Ningxin Ge, Kan Suzuki, Iori Sato, Michiya Noguchi, Yukio Nakamura, Mami Matsuo-Takasaki, Jun Fujishiro, Yohei Hayashi
{"title":"Generation of human induced pluripotent stem cell lines derived from patients of cystic biliary atresia.","authors":"Ningxin Ge, Kan Suzuki, Iori Sato, Michiya Noguchi, Yukio Nakamura, Mami Matsuo-Takasaki, Jun Fujishiro, Yohei Hayashi","doi":"10.1007/s13577-024-01147-x","DOIUrl":"10.1007/s13577-024-01147-x","url":null,"abstract":"<p><p>Biliary atresia (BA), resulting from abnormal development of the liver's internal or external bile ducts, can lead to liver damage and potentially fatal cirrhosis. Type I cystic biliary atresia is a relatively uncommon, but clinically significant variant of BA. It is critical to develop experimental models of BA to examine the etiology and pathogenesis, which remain elusive, and to develop future therapeutics. Here, we have successfully generated a panel of human induced pluripotent stem cells (hiPSCs) from five Japanese patients carrying type I cystic BA. These hiPSC lines exhibited characteristics of self-renewal and pluripotency. These cells held normal karyotypes mostly, but one of them carried hemizygous deletions, the clinical significance of which is unknown yet. Whole genome sequence analysis indicated that some of the mutations or single nucleotide polymorphisms (SNPs) commonly found in these patients are related to hepatobiliary abnormality. Given the limited understanding of the molecular pathogenesis of cystic BA, attributed to unknown factors of genetic and environmental causes, these cellular resources will be instrumental in replicating disease phenotypes and in advancing novel therapies for this disease.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 1","pages":"18"},"PeriodicalIF":3.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631013","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 : 2024-11-12DOI: 10.1007/s13577-024-01144-0
Tao Wang, Lin Ye, Yingjie Zhou, Xionghan Zhang, Renjian Li, Yi Zhou, Jun Weng, Qingrong Mo, Yaqun Yu
{"title":"Pancreatic cancer-derived exosomal miR-510 promotes macrophage M2 polarization and facilitates cancer cell aggressive phenotypes.","authors":"Tao Wang, Lin Ye, Yingjie Zhou, Xionghan Zhang, Renjian Li, Yi Zhou, Jun Weng, Qingrong Mo, Yaqun Yu","doi":"10.1007/s13577-024-01144-0","DOIUrl":"10.1007/s13577-024-01144-0","url":null,"abstract":"<p><p>Extensive tumor microenvironment (TME) and tumor-associated macrophages (TAMs) contribute to the initiation and progression of pancreatic cancer (PC). Cancer cell-derived exosomal miRNAs that stimulate macrophage M2 polarization might play an important role in the process. In the current study, we observed significant upregulation of miR-510 in PC cell lines in comparison to normal HPDE cell line, with PANC-1 exhibiting the highest and MIA PaCa-2 the lowest miR-510 levels. Functional assays demonstrated that miR-510 overexpression enhanced, while its inhibition reduced, PC cell viability, migration, invasion, and EMT. In vivo, miR-510 mimics promoted tumor growth and macrophage M2 polarization, whereas miR-510 inhibition had the opposite effect. Exosomes from PANC-1 and MIA PaCa-2 cells, characterized by nanoparticle tracking analysis and TEM, contained significantly higher miR-510 levels than those from HPDE cells. Macrophages incubated with conditioned media from these PC cells showed increased M2 polarization markers, a process inhibited by the exosome inhibitor GW4869. The delivery of miR-510 via PC cell-derived exosomes facilitated macrophage M2 polarization and regulated the STAT signaling pathway, suggesting that exosomal miR-510 plays a crucial role in the tumor microenvironment of PC by modulating macrophage M2 polarization.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 1","pages":"17"},"PeriodicalIF":3.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631020","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 : 2024-11-06DOI: 10.1007/s13577-024-01145-z
Pan Han, Xinxin Zhao, Xuexun Li, Jing Geng, Shouxiang Ni, Qiao Li
{"title":"Pathophysiology, molecular mechanisms, and genetics of atrial fibrillation.","authors":"Pan Han, Xinxin Zhao, Xuexun Li, Jing Geng, Shouxiang Ni, Qiao Li","doi":"10.1007/s13577-024-01145-z","DOIUrl":"10.1007/s13577-024-01145-z","url":null,"abstract":"<p><p>The development of atrial fibrillation (AF) is a highly complex, multifactorial process involving pathophysiologic mechanisms, molecular pathway mechanisms and numerous genetic abnormalities. The pathophysiologic mechanisms including altered ion channels, abnormalities of the autonomic nervous system, inflammation, and abnormalities in Ca2 + handling. Molecular pathway mechanisms including, but not limited to, renin-angiotensin-aldosterone (RAAS), transforming growth factor-β (TGF-β), oxidative stress (OS). Although in clinical practice, the distinction between types of AF such as paroxysmal and persistent determines the choice of treatment options. However, it is the pathophysiologic alterations present in AF that truly determine the success of AF treatment and prognosis, but even more so the molecular mechanisms and genetic alterations that lie behind them. One tiny clue reveals the general trend, and small beginnings show how things will develop. This article will organize the development of these mechanisms and their interactions in recent years.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 1","pages":"14"},"PeriodicalIF":3.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591895","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 : 2024-11-04DOI: 10.1007/s13577-024-01139-x
Jiao Deng, Jerry H Qin, Xiaolan Li, Deding Tao, Yongdong Feng
{"title":"Establishment and drug resistance characterization of paired organoids using human primary colorectal cancer and matched tumor deposit specimens.","authors":"Jiao Deng, Jerry H Qin, Xiaolan Li, Deding Tao, Yongdong Feng","doi":"10.1007/s13577-024-01139-x","DOIUrl":"10.1007/s13577-024-01139-x","url":null,"abstract":"<p><p>Tumor deposits (TDs) represent a specific form tumor metastasis observed in colorectal cancer (CRC). The lack of successfully established cell lines for TDs, as well as the molecular mechanisms by which TDs occur remain largely unknown. Here, we established paired CRC organoids, including a human primary cancer organoid and its TD organoid, from a 46-year-old male patient with CRC. Further analysis revealed that, compared with primary tumor-derived cells, TD-derived cells exhibited enhanced proliferative, invasive and metastatic capabilities, and increased expression of stemness-related proteins. Furthermore, the present findings also demonstrated that TD-derived cells were more resistant to oxaliplatin or 5-FU. Transcriptomic profiling and qPCR revealed that TD-derived cells exhibited more alterations in fatty acid metabolism signaling and enhanced lipid synthesis ability compared to primary tumor-derived cells. Inhibition of lipid synthesis markedly decreased resistance to oxaliplatin in TD-derived cells. Taken together, the paired organoids established using CRC primary tumor and its TD specimens will provide valuable tools to study tumorigenicity, metastasis and chemoresistance in CRC. Notably, these models will provide novel insights to study tumor heterogeneity and lipid metabolism in CRC.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 1","pages":"13"},"PeriodicalIF":3.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570121","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}