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Phillygenin regulates the colorectal cancer tumor microenvironment by inhibiting hypoxia-inducible factor 1 alpha.
IF 2 4区 生物学
Cytotechnology Pub Date : 2025-02-01 Epub Date: 2024-12-10 DOI: 10.1007/s10616-024-00679-2
Tianhao Chu, Yidi Ning, Mingqian Ma, Zhenying Zhao, Jun Liu, Wei Wang, Xueer Yu, Yijia Wang, Shiwu Zhang
{"title":"Phillygenin regulates the colorectal cancer tumor microenvironment by inhibiting hypoxia-inducible factor 1 alpha.","authors":"Tianhao Chu, Yidi Ning, Mingqian Ma, Zhenying Zhao, Jun Liu, Wei Wang, Xueer Yu, Yijia Wang, Shiwu Zhang","doi":"10.1007/s10616-024-00679-2","DOIUrl":"10.1007/s10616-024-00679-2","url":null,"abstract":"<p><p>The tumor microenvironment (TME) is important in the recurrence and metastasis of colorectal cancer (CRC). Phillygenin is an effective component of <i>Forsythiae fructus</i> that has long been used in cancer therapy. The mechanism by which phillygenin regulates the TME remains unknown. Methods and Results: A co-culture system of CRC cells and Jurkat T cells was used to simulate the TME <i>in vitro</i>. Network pharmacology and Human XL cytokine arrays were used to preliminarily evaluate the role of phillygenin in the TME. The target of phillygenin was determined using transfection of plasmid-producing overexpression of hypoxia-inducible factor 1 alpha (HIF-1α) overexpression or abrogated HIF-1α expression via short hairpin RNA plasmid. The therapeutic effect of phillygenin <i>in vivo</i> was assessed in a subcutaneous tumor mouse model. <i>In vitro</i>, phillygenin enhanced the immune response of T cells and prevented the immune escape of cancer cells via the inhibition of HIF-1α. Phillygenin upregulated interleukin (IL)-2 and downregulates IL-10 and FOXP3 in Jurkat T cells co-cultured with CRC cells. Phillygenin inhibited expressions of HIF-1α, transforming growth factor-beta, vascular endothelial growth factor, and CD31 in CRC cells cultured alone or with Jurkat T cells. Phillygenin considerably suppressed tumor growth and improved the TME <i>in vivo</i>. Conclusions: Phillygenin can enhance the immune response and inhibit angiogenesis in the TME in CRC by inhibiting HIF-1α.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s10616-024-00679-2.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"77 1","pages":"17"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Game-changing breakthroughs to redefine the landscape of the renin-angiotensin-aldosterone system in health and disease. 改变游戏规则的突破,重新定义肾素-血管紧张素-醛固酮系统在健康和疾病中的作用。
IF 4.4 2区 生物学
Cellular signalling Pub Date : 2025-02-01 Epub Date: 2024-10-09 DOI: 10.1016/j.cellsig.2024.111459
Pitchai Balakumar, Gowraganahalli Jagadeesh
{"title":"Game-changing breakthroughs to redefine the landscape of the renin-angiotensin-aldosterone system in health and disease.","authors":"Pitchai Balakumar, Gowraganahalli Jagadeesh","doi":"10.1016/j.cellsig.2024.111459","DOIUrl":"10.1016/j.cellsig.2024.111459","url":null,"abstract":"<p><p>Novel perspectives on the role of the renin-angiotensin-aldosterone system (RAAS) offer a groundbreaking understanding of the system's role in health and illness. Our understanding of the role of the RAAS in several diseases, such as heart failure, hypertension, metabolic disorders, and chronic renal disease, has been broadened by recent studies. Specific variations in RAAS pathways can affect the course of disease and response to treatment, as shown by genetic and molecular research. The dynamic and fast-evolving nature of RAAS research described in this special issue might transform our approach to managing renal, neurological, and cardiovascular health, among other disease conditions, including cancer.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"111459"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of pH on antitumor activity of Chinese cobra (Naja atra) cytotoxin-XII. pH 值对眼镜蛇细胞毒素-XII 抗肿瘤活性的影响
IF 2 4区 生物学
Cytotechnology Pub Date : 2025-02-01 Epub Date: 2024-12-13 DOI: 10.1007/s10616-024-00681-8
Xiancai Su, Jiayi Zhou, Mingyuan Zhang, Xiaoping Kang, Dongli Lu, Yanling Chen, Qing Lin, Cailing Yan, Yunlu Xu
{"title":"Effect of pH on antitumor activity of Chinese cobra (Naja atra) cytotoxin-XII.","authors":"Xiancai Su, Jiayi Zhou, Mingyuan Zhang, Xiaoping Kang, Dongli Lu, Yanling Chen, Qing Lin, Cailing Yan, Yunlu Xu","doi":"10.1007/s10616-024-00681-8","DOIUrl":"10.1007/s10616-024-00681-8","url":null,"abstract":"<p><p>Cytotoxins (CTXs), proteins found in cobra venom, selectively inhibit tumor cell proliferation. Herein, we selected CTX-XII because of its potent antitumor activity to investigate the effect of solution pH on its response. MTT assay results showed significantly higher inhibition rates for CTX-XII at pH 5.72 (75.79 ± 3.48%) than that at pH 7.32 (50.75 ± 3.8%). Flow cytometry demonstrated that apoptosis rates in B16F10 cells induced by CTX-XII were also higher at pH 5.72 (44.92 ± 7.94%) and 4.12 (42.87 ± 1.89%) than at pH 7.32 (23.5 ± 4.02%). Confocal laser scanning microscopy images showed that red fluorescence, representing CTX-XII concentration, was more intense around tumor cells at pH 5.72, with higher levels in the cytoplasm, than at pH 7.32. In the murine melanoma model, tumor weight in the pH 5.72 CTX-XII group (0.45 ± 0.19 g) was significantly lower than that in the pH 7.32 CTX-XII group (0.84 ± 0.42 g). These results indicate that pH has a strong influence on the antitumor activity of CTX-XII, likely due to pH-dependent ionization changes in CTX-XII that increase its affinity for and penetration into tumor cell membranes. This study provides new insights into the antitumor effects of CTXs and factors influencing their activity.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s10616-024-00681-8.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"77 1","pages":"21"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Docetaxel treatment together with CTLA-4 knockdown enhances reduction of cell viability and amplifies apoptosis stimulation of MCF-7 breast cancer cells. 多西他赛治疗和 CTLA-4 基因敲除可增强 MCF-7 乳腺癌细胞活力的降低和凋亡刺激的扩大。
IF 2 4区 生物学
Cytotechnology Pub Date : 2025-02-01 Epub Date: 2024-12-12 DOI: 10.1007/s10616-024-00677-4
Negar Hosseinkhani, Shiva Alipour, Amir Ghaffari Jolfayi, Leili Aghebati-Maleki, Elham Baghbani, Nazila Alizadeh, Vahid Khaze, Behzad Baradaran
{"title":"Docetaxel treatment together with CTLA-4 knockdown enhances reduction of cell viability and amplifies apoptosis stimulation of MCF-7 breast cancer cells.","authors":"Negar Hosseinkhani, Shiva Alipour, Amir Ghaffari Jolfayi, Leili Aghebati-Maleki, Elham Baghbani, Nazila Alizadeh, Vahid Khaze, Behzad Baradaran","doi":"10.1007/s10616-024-00677-4","DOIUrl":"https://doi.org/10.1007/s10616-024-00677-4","url":null,"abstract":"<p><p>Breast cancer is the most frequent cancer in women with a 20% mortality rate. The fate of patients suffering from breast cancer can be influenced by immune cells and tumor cells interaction in the tumor microenvironment (TME). Immune checkpoints such as Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) are regulators of the immune system and defend normal tissues from immune cell attacks but they can be expressed in breast cancer tissue and facilitate immune evasion of tumoral cells. Based on this, here we studied the role of CTLA-4 silencing by specific siRNA in MCF-7 breast cancer cell line together with Docetaxel treatment which is one of the robust chemotherapy agents to demonstrate the significance of combining chemotherapy with efficient targeted therapy in tumor regression. The MCF-7 breast cancer cell line was transfected with CTLA-4-siRNA through the electroporation method, then received an appropriate dose of Docetaxel determined by MTT assay. Flow cytometry was utilized to investigate the consequence of simultaneous CTLA-4 gene silencing and Docetaxel treatment on the apoptosis and cell cycle of MCF-7 cells. The expression levels of Bax and Bcl-2 were also investigated using quantitative real-time PCR. Compared to control groups, CTLA-4-suppressed and Docetaxel-treated cells became more susceptible to apoptosis and cell cycle arrest at the G2-M phase. The additive effect of CTLA-4 knockdown together with Docetaxel treatment significantly downregulated BCL-2 level and upregulated BAX expression. Our findings support the idea that combining chemotherapy such as Docetaxel with efficient targeted therapy against inhibitory immune checkpoints can be a promising strategy in cancer treatment.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"77 1","pages":"19"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
History and genetic diversity of African sheep: Contrasting phenotypic and genomic diversity. 非洲绵羊的历史和遗传多样性:表型和基因组多样性的对比。
IF 1.8 3区 生物学
Animal genetics Pub Date : 2025-02-01 Epub Date: 2024-11-19 DOI: 10.1111/age.13488
Anne Da Silva, Abulgasim Ahbara, Imen Baazaoui, Slim Ben Jemaa, Yinhong Cao, Elena Ciani, Edgar Farai Dzomba, Linda Evans, Elisha Gootwine, Olivier Hanotte, Laura Harris, Meng-Hua Li, Salvatore Mastrangelo, Ayao Missohou, Annelin Molotsi, Farai C Muchadeyi, Joram M Mwacharo, Gaëlle Tallet, Pascal Vernus, Stephen J G Hall, Johannes A Lenstra
{"title":"History and genetic diversity of African sheep: Contrasting phenotypic and genomic diversity.","authors":"Anne Da Silva, Abulgasim Ahbara, Imen Baazaoui, Slim Ben Jemaa, Yinhong Cao, Elena Ciani, Edgar Farai Dzomba, Linda Evans, Elisha Gootwine, Olivier Hanotte, Laura Harris, Meng-Hua Li, Salvatore Mastrangelo, Ayao Missohou, Annelin Molotsi, Farai C Muchadeyi, Joram M Mwacharo, Gaëlle Tallet, Pascal Vernus, Stephen J G Hall, Johannes A Lenstra","doi":"10.1111/age.13488","DOIUrl":"10.1111/age.13488","url":null,"abstract":"<p><p>Domesticated sheep have adapted to contrasting and extreme environments and continue to play important roles in local community-based economies throughout Africa. Here we review the Neolithic migrations of thin-tailed sheep and the later introductions of fat-tailed sheep into eastern Africa. According to contemporary pictorial evidence, the latter occurred in Egypt not before the Ptolemaic period (305-25 BCE). We further describe the more recent history of sheep in Egypt, the Maghreb, west and central Africa, central-east Africa, and southern Africa. We also present a comprehensive molecular survey based on the analysis of 50 K SNP genotypes for 59 African breeds contributed by several laboratories. We propose that gene flow and import of fat-tailed sheep have partially overwritten the diversity profile created by the initial migration. We found a genetic contrast between sheep north and south of the Sahara and a west-east contrast of thin- and fat-tailed sheep. There is no close relationship between African and central and east Asian fat-tailed breeds, whereas we observe within Africa only a modest effect of tail types on breed relationships.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":" ","pages":"e13488"},"PeriodicalIF":1.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674939","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}
引用次数: 0
IBS008738, a TAZ activator, facilitates muscle repair and inhibits muscle injury in a mouse model of sport-induced injury. IBS008738 是一种 TAZ 激活剂,它能促进小鼠运动损伤模型中的肌肉修复并抑制肌肉损伤。
IF 2 4区 生物学
Cytotechnology Pub Date : 2025-02-01 Epub Date: 2024-11-19 DOI: 10.1007/s10616-024-00667-6
Yiming Wang, Datian Liu, Sining Wang, Yiliang Li, Guanming Liu
{"title":"IBS008738, a TAZ activator, facilitates muscle repair and inhibits muscle injury in a mouse model of sport-induced injury.","authors":"Yiming Wang, Datian Liu, Sining Wang, Yiliang Li, Guanming Liu","doi":"10.1007/s10616-024-00667-6","DOIUrl":"10.1007/s10616-024-00667-6","url":null,"abstract":"<p><p>High-intensity exercise can cause excessive generation of ROS and induce oxidative stress injury in the body, which is a major reason accounting for muscle damage following exercise. The previous study demonstrated that IBS008738, the activator of TZA, was able to enhance myogenesis in mouse myogenic C2C12 cells, prevent dexamethasone-induced muscle atrophy, and facilitate muscle repair in cardiotoxin-induced muscle injury. Accordingly, our study was designed to probe into the potential role of IBS008738 in muscle damage in mouse models induced by high-intensity exercise. Mice were first administrated with IBS008738, and then subjected to high-intensity eccentric exercise to induce muscle damage after 24 h. During the experiment, mouse weight change and food take were recorded. At the end of the experiment, blood samples were collected through cardiac puncture and centrifugated. Serum levels of blood urea nitrogen (BUN), creatinine, glucose, lactate dehydrogenase (LDH), creatinine kinase (CK), and C-related protein were evaluated using an autoanalyzer. After mice were sacrificed, the gastrocnemius muscles were dissected for DCFH-DA assay of ROS generation, thiobarbituric acid-reactive substances (TBARS) assay of MDA content, hematoxylin-eosin (H&E) staining of histological examination, and western blotting analysis of Akt/mTOR/S6K1 signaling expression. IBS008738 and/or exercise exert significant effects on mouse weight and food take. High-intensity exercise markedly increased ROS generation and lipid peroxidation, upregulated serum levels of CK, LDH, and C-related protein, ameliorated muscle histological damage, and reduced TAZ, phosphorylated (p)-Akt, p-mTOR, and p-S6K1 protein levels in mice. However, IBS008738 administration reversed the above changes induced by high-intensity exercise in mice. IBS008738 alleviates oxidative stress and muscle damage in mice after high-intensity exercise by activating TAZ and the Akt/mTOR/S6K1 signaling pathway.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s10616-024-00667-6.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"77 1","pages":"2"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analysis of cell lysis for improved understanding between the shake tube and stirred tank reactor perfusion CHO cell cultures.
IF 2 4区 生物学
Cytotechnology Pub Date : 2025-02-01 Epub Date: 2024-11-27 DOI: 10.1007/s10616-024-00662-x
Weijian Zhang, Qingyuan Ran, Yang Zhou, Liang Zhao, Qian Ye, Wen-Song Tan
{"title":"Analysis of cell lysis for improved understanding between the shake tube and stirred tank reactor perfusion CHO cell cultures.","authors":"Weijian Zhang, Qingyuan Ran, Yang Zhou, Liang Zhao, Qian Ye, Wen-Song Tan","doi":"10.1007/s10616-024-00662-x","DOIUrl":"https://doi.org/10.1007/s10616-024-00662-x","url":null,"abstract":"<p><p>Shake tubes (ST) are widely employed to assist the development of the stirred tank reactor (STR) perfusion cell culture. However, cell lysis may be frequently underrestimated and lead to culture performance discrepency between these systems, rendering the ST model ineffective in designing the STR perfusion cultures. In this study, perfusion culture performance bewteen the STR and ST was investigated under various conditions with the analysis of cell lysis. Comparable performance was observed bewteen the two systems at low perfusion rates ( <math><mi>D</mi></math> ≤1.0 VVD), except that the specific productivity ( <math><msub><mi>q</mi> <mi>P</mi></msub> </math> ) of the STR was decreased at <math><mi>D</mi></math> =0.5 VVD, which was related to product degradation by cell lysis. In contrast, significant differences in cell maintenance, metabolism, and <math><msub><mi>q</mi> <mi>P</mi></msub> </math> were found at <math><mi>D</mi></math> =2.0 VVD. By the analysis of the authentic cell growth and death kinetics, it was found that cell growth arrest, potentially due to the limited availability of oxygen, led to the stable cell maintenance at VCD≈90 × 10<sup>6</sup> cells/ml and altered cellular metabolism for the ST, while the continuous decline of VCD and <math><msub><mi>q</mi> <mi>P</mi></msub> </math> in the STR were related to excessive cell death, subsequently ascribed to the harmful hydrodynamic stress conditions. We further demonstrated that cell lysis accounted for 57.62-76.29% of the total generated biomass in both the reactors and significantly impacted the estimation of process descriptors crucial for understanding the true cellular states. With cell lysis in sight, cell performance can therefore be accurately described and this knowledge can be further leveraged to expedite process development for the perfusion cell culture processes.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"77 1","pages":"7"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to "Monomeric copper(II) complexes with unsymmetrical salen environment: Synthesis, characterization and study of biological activities" [Journal of Inorganic Biochemistry 253 (2024) 112497]. 具有非对称沙林环境的单体铜(II)配合物:合成、表征和生物活性研究" [《无机生物化学杂志》253 (2024) 112497]。
IF 3.8 2区 化学
Journal of Inorganic Biochemistry Pub Date : 2025-02-01 Epub Date: 2024-10-05 DOI: 10.1016/j.jinorgbio.2024.112753
Deepika Mohapatra, Sushree Aradhana Patra, Pratikshya Das Pattanayak, Gurunath Sahu, Takashi Nakamura, Takahiro Sasamori, Rupam Dinda
{"title":"Corrigendum to \"Monomeric copper(II) complexes with unsymmetrical salen environment: Synthesis, characterization and study of biological activities\" [Journal of Inorganic Biochemistry 253 (2024) 112497].","authors":"Deepika Mohapatra, Sushree Aradhana Patra, Pratikshya Das Pattanayak, Gurunath Sahu, Takashi Nakamura, Takahiro Sasamori, Rupam Dinda","doi":"10.1016/j.jinorgbio.2024.112753","DOIUrl":"10.1016/j.jinorgbio.2024.112753","url":null,"abstract":"","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":" ","pages":"112753"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Aging and cell expansion enhance microRNA diversity in small extracellular vesicles produced from human adipose-derived stem cells.
IF 2 4区 生物学
Cytotechnology Pub Date : 2025-02-01 Epub Date: 2024-12-10 DOI: 10.1007/s10616-024-00675-6
Toshiya Tsubaki, Ryota Chijimatsu, Taiga Takeda, Maki Abe, Takahiro Ochiya, Shinsaku Tsuji, Keita Inoue, Tokio Matsuzaki, Yasuhide Iwanaga, Yasunori Omata, Sakae Tanaka, Taku Saito
{"title":"Aging and cell expansion enhance microRNA diversity in small extracellular vesicles produced from human adipose-derived stem cells.","authors":"Toshiya Tsubaki, Ryota Chijimatsu, Taiga Takeda, Maki Abe, Takahiro Ochiya, Shinsaku Tsuji, Keita Inoue, Tokio Matsuzaki, Yasuhide Iwanaga, Yasunori Omata, Sakae Tanaka, Taku Saito","doi":"10.1007/s10616-024-00675-6","DOIUrl":"10.1007/s10616-024-00675-6","url":null,"abstract":"<p><p>Adipose-derived stem cells (ASCs) and their small extracellular vesicles (sEVs) hold significant potential for regenerative medicine due to their tissue repair capabilities. The microRNA (miRNA) content in sEVs varies depending on ASC status; however, the effects of aging and cell passage on miRNA profiles remain unclear. In this study, we examined the effects of donor age and cell expansion on ASC characteristics and transcriptome using ASCs obtained from three young and three old donors. Cell expansion significantly impaired stem cell properties, notably reducing proliferation and differentiation capacities. In contrast, donor age had minimal effects on ASCs. RNA sequencing (RNA-seq) revealed differences in gene expression related to stemness, phagocytosis, and metabolic processes influenced by cell expansion. To investigate miRNA variability, we performed small RNA-seq on sEVs collected from ASCs of all six donors. The miRNA profiles were influenced by donor age and cell passage. Interestingly, functional enrichment analysis indicated that advanced donor age and increased cell passage may enhance the production of miRNAs associated with organ development through various pathways. These findings suggest that donor age and cell expansion differentially influence ASC characteristics and sEV miRNA content, highlighting the need for disease-specific conditioning of ASCs to optimize the therapeutic effects of sEVs in clinical applications.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s10616-024-00675-6.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"77 1","pages":"15"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparing the growth kinetics and characteristics of Wharton's jelly derived mesenchymal stem cells expanded using different culture mediums.
IF 2 4区 生物学
Cytotechnology Pub Date : 2025-02-01 Epub Date: 2024-12-19 DOI: 10.1007/s10616-024-00682-7
Muhammad Najib Fathi Hassan, Muhammad Dain Yazid, Mohd Heikal Bin Mohd Yunus, Yogeswaran Lokanathan, Min Hwei Ng, Ruszymah Bt Hj Idrus, Yee Loong Tang, See Nguan Ng, Jia Xian Law
{"title":"Comparing the growth kinetics and characteristics of Wharton's jelly derived mesenchymal stem cells expanded using different culture mediums.","authors":"Muhammad Najib Fathi Hassan, Muhammad Dain Yazid, Mohd Heikal Bin Mohd Yunus, Yogeswaran Lokanathan, Min Hwei Ng, Ruszymah Bt Hj Idrus, Yee Loong Tang, See Nguan Ng, Jia Xian Law","doi":"10.1007/s10616-024-00682-7","DOIUrl":"https://doi.org/10.1007/s10616-024-00682-7","url":null,"abstract":"<p><p>Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) can be isolated from umbilical cords which is abundant and easy to obtain. Due to their potent immunosuppressive properties, multilineage differentiation potential, and lack of ethical issues, WJ-MSCs are considered a promising candidate for therapeutic applications. However, large-scale in vitro expansion is necessary to obtain enough cells for therapeutic purposes. Therefore, this study aimed to optimize cell culture conditions and determine the characteristics of expanded WJ-MSCs. WJ-MSCs were seeded in 6-well plates at a density of 5000 cells/cm<sup>2</sup> and cultured with different mediums, including DMEM-LG+10% FBS, DMEM-LG+10% HPL, serum-free commercial medium 1, serum-free GMP grade commercial medium 2, and HPL supplemented commercial medium 3. The cell morphology and growth kinetics were compared, and the three most suitable mediums were selected for further experiments. WJ-MSCs were then cultured in the selected mediums at seeding densities ranging from 1000 to 5000 cells/cm<sup>2</sup>, and cell growth kinetics were analysed. WJ-MSCs cultured in the selected mediums were characterized by their immunophenotype, tri-lineage differentiation potential and immunosuppression property. WJ-MSCs cultured with DMEM-LG+10% HPL, commercial medium 1 and commercial medium 2 showed smaller size, significantly higher cell yield, and shorter population doubling time than those cultured in other mediums. Hence, these three mediums were selected for further experiments. Only DMEM-LG + 10% HPL medium maintained high cell yields (1.48 ± 0.14 × 10<sup>6</sup> with bFGF and 1.56 ± 0.17 × 10<sup>6</sup> without bFGF) at the lowest seeding density tested. However, WJ-MSCs cultured in all three mediums expressed the MSC surface markers, were able to suppress PBMC proliferation, and could differentiate into adipogenic, chondrogenic and osteogenic lineages. In summary, DMEM-LG+10% HPL is the best medium for WJ-MSC expansion, as it provides the highest cell yield without compromising cell characteristics and functionality. The potential of this medium for large-scale expansion using a bioreactor or multilayered flask should be investigated in the future.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"77 1","pages":"24"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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