Cellular and molecular bioengineering最新文献

{"title":"Macrophage Polarization Profiling in Dynamic Culture System.","authors":"Alperen Yılmaz, Resul Özbilgiç, Elifsu Polatlı, İbrahim Halilullah Erbay, Duygu Sağ, Sinan Güven","doi":"10.1007/s12195-025-00863-0","DOIUrl":"https://doi.org/10.1007/s12195-025-00863-0","url":null,"abstract":"<p><strong>Purpose: </strong>In this study, we aimed to develop a dynamic on-chip platform to study macrophage polarization in a more physiologically relevant way by incorporating mechanical forces which have been recently shown to play important roles in macrophage biology.</p><p><strong>Methods: </strong>We developed polymethyl methacrylate (PMMA) based platform. We examined the effects of the dynamic microenvironment on polarization states of human monocyte derived macrophages (HMDMs) towards the M1 and M2a phenotypes using lipopolysaccharide (LPS)/interferon-γ (IFN-γ) and interleukin-4 (IL-4) respectively for both static and dynamic conditions. M1 and M2 polarization levels were assessed by qPCR and flow cytometry analyses.</p><p><strong>Results: </strong>M1 and M2 polarization was achieved successfully under dynamic and static conditions. Our platform establishes that the mechanotransductive stimulation through shear stress during polarization has direct synergistic effects with stimulants on TNF-α secretion within HMDMs. Exposure to media flow rates of 0.5, 2.5, and 5 µl/min without stimulants is insufficient to induce macrophage polarization.</p><p><strong>Conclusion: </strong>The dynamic environment present inside our dynamic on-chip culture platform influences the human monocyte-derived macrophages (HMDMs) to become polarized into M1 phenotype at a greater level.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-025-00863-0.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"18 3-4","pages":"311-322"},"PeriodicalIF":5.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered Extracellular Vesicles for Targeted Paclitaxel Delivery in Cancer Therapy: Advances, Challenges, and Prospects.","authors":"Mohamed J Saadh, Hanan Hassan Ahmed, Radhwan Abdul Kareem, Ashishkumar Kyada, H Malathi, Deepak Nathiya, Deepak Bhanot, Waam Mohammed Taher, Mariem Alwan, Mahmood Jasem Jawad, Atheer Khdyair Hamad","doi":"10.1007/s12195-025-00858-x","DOIUrl":"https://doi.org/10.1007/s12195-025-00858-x","url":null,"abstract":"<p><strong>Scope: </strong>Extracellular vesicles (EVs) have emerged as promising cell-free delivery vehicles for cancer therapy due to their inherent biocompatibility, low immunogenicity, and natural targeting capabilities. EVs derived from various cellular sources offer distinct advantages in drug-loading capacity and therapeutic effectiveness. However, their clinical application is limited by challenges such as poor cargo stability, potential immunogenicity, and off-target effects. These limitations necessitate further surface functionalization of EVs to optimize vesicle stability, targeting precision, and safety of pharmacological cargos. Paclitaxel (PTX), a first-line chemotherapeutic agent effective against multiple cancers, is limited by poor solubility and significant systemic toxicity, highlighting the need for targeted delivery systems.</p><p><strong>Methods: </strong>A literature search was conducted to identify relevant articles published between 1993 and 2025. This review provides a comprehensive overview of EV biogenesis and cellular origins, highlighting recent advances in engineering strategies for PTX delivery. Current progress in employing engineered EVs for PTX delivery in both in vitro and in vivo cancer models, along with practical challenges and future directions in the clinical translation of EV-based PTX delivery, are discussed.</p><p><strong>Results: </strong>Preclinical studies demonstrate that engineered EVs can effectively encapsulate and deliver PTX to tumor sites, improving therapeutic outcomes while minimizing systemic side effects. Despite these advances, challenges remain in optimizing EV isolation, surface modification, PTX loading efficiency, and precise recognition of tumor cells.</p><p><strong>Conclusion: </strong>Engineered EVs represent a promising platform for PTX delivery, combining targeted therapeutic potential with reduced systemic toxicity. Continued research to address technical and translational barriers will be critical for advancing EV-based PTX therapies toward clinical application.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"18 3-4","pages":"213-237"},"PeriodicalIF":5.0,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>WNT7A</i> mRNA Lipid Nanoparticles Promote Muscle Hypertrophy and Reduce Fatty Infiltration.","authors":"Larion Martin Santiago, Kasoorelope Oguntuyo, Britney Chin-Young, Damien Laudier, Zhixin Yu, Pedro Henrique Alves da Silva, Fei Fang, Angelo Amabile, Woojin M Han","doi":"10.1007/s12195-025-00859-w","DOIUrl":"10.1007/s12195-025-00859-w","url":null,"abstract":"<p><strong>Purpose: </strong>Myosteatosis and muscle atrophy are key pathological features of skeletal muscle degeneration in chronic injuries, degenerative myopathies, and aging. While recombinant WNT7A has shown promise in stimulating muscle hypertrophy and reducing fatty infiltration, its clinical translation is limited by challenges in delivery, scalability, and cost. The objective of this study was to evaluate the feasibility of lipid nanoparticle (LNP)-mediated mRNA delivery of WNT7A (W7a-LNP) as an alternative strategy for mitigating muscle degeneration.</p><p><strong>Methods: </strong>W7a-LNP efficacy was assessed <i>in vitro</i> and <i>in vivo</i> using primary murine fibro-adipogenic progenitors (FAPs), C2C12 myoblasts, and mouse models of muscle injury. FAP adipogenesis and myofiber size were quantified following W7a-LNP treatment. <i>In vivo</i>, W7a-LNP was administered via intramuscular injection in uninjured and glycerol-injured muscles, and its effects on myofiber size and intramuscular adipose tissue (IMAT) formation were analyzed.</p><p><strong>Results: </strong>W7a-LNP inhibited adipogenesis and increased myofiber size <i>in vitro</i>. In uninjured muscle, multiple W7a-LNP injections significantly increased myofiber size without inducing fibrosis, confirming its safety and efficacy in promoting muscle hypertrophy. However, in the glycerol injury model, W7a-LNP treatment showed variable effects on IMAT reduction when delivered early post-injury, likely due to the absence of viable myofibers needed for mRNA uptake and protein production. Delayed delivery at 4 days post-injury significantly reduced fatty infiltration, supporting the importance of timing and target cell availability for therapeutic efficacy.</p><p><strong>Conclusions: </strong>These findings provide proof-of-concept that W7a-LNP enhances myofiber hypertrophy and modulates fatty infiltration, supporting mRNA LNP technology as a scalable and localized alternative to recombinant protein therapy for combating muscle degeneration. Further optimization of dose, delivery frequency, and biodistribution will be critical for clinical translation.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12431683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Pluripotency and Adipogenic Differentiation in Human Adipose Tissue-Derived Stem Cells Through miR-302/367 Cluster Overexpression.","authors":"Hossein Faghih, Maryam Khani, Mehdi Shamsara, Hossein Taghizadeh, Arash Javeri, Masoumeh Fakhr Taha","doi":"10.1007/s12195-025-00856-z","DOIUrl":"https://doi.org/10.1007/s12195-025-00856-z","url":null,"abstract":"<p><strong>Purpose: </strong>Human adipose tissue-derived stem cells (hADSCs) have emerged as a promising source of cells for tissue engineering and regenerative medicine. However, their differentiation potential is restricted and requires enhancements. This study explores the reprogramming of hADSCs through exogenous induction of the miR-302/367 cluster.</p><p><strong>Methods: </strong>Human ADSCs were transfected with the mock or miR-302/367 cluster-expressing vectors. One week after transfection, expression levels of several pluripotency-related genes, epithelial-to-mesenchymal (EMT) markers, and mechanistic target of rapamycin kinase (mTOR) signaling factors were assessed by qPCR and western blot. Additionally, the influence of miR-302/367 cluster overexpression on the proliferation and adipogenic differentiation of the ADSCs was evaluated.</p><p><strong>Results: </strong>One week after transfection, the expression of several pluripotency-related genes and epithelial markers was significantly upregulated, while mesenchymal markers were downregulated in the miR-302/367-transfected cells compared with the mock group. Additionally, the levels of several mTOR signaling factors were reduced in the miR-302/367-transfected ADSCs. Flow cytometry analysis showed a decrease in the abundance of ADSCs in the S phase and an increase in the population of cells in the G1 phase of the cell cycle. Moreover, the adipogenic differentiation of the miR-302/367-transfected cells was significantly enhanced.</p><p><strong>Conclusion: </strong>The overexpression of the miR-302/367 cluster directed the ADSCs towards a more pluripotent state and promoted their adipogenic potential. However, miR-302/367 overexpression diminished the proliferative capacity of hADSCs, which warrants a comprehensive investigation. Further evaluations are needed to fully elucidate the differentiation potential and regenerative capacity of the ADSCs reprogrammed by the miR-302/367 cluster before any clinical application.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-025-00856-z.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"18 3-4","pages":"297-309"},"PeriodicalIF":5.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Cell-Derived Plasma Membrane Vesicles as a Nanoparticle Encapsulation and Delivery System.","authors":"Mahsa Kheradmandi, Amir M Farnoud, Monica M Burdick","doi":"10.1007/s12195-025-00854-1","DOIUrl":"10.1007/s12195-025-00854-1","url":null,"abstract":"<p><strong>Purpose: </strong>Developing non-invasive delivery platforms with a high level of structural and/or functional similarity to biological membranes is highly desirable to reduce toxicity and improve targeting capacity of nanoparticles. Numerous studies have investigated the impacts of physicochemical properties of engineered biomimetic nanoparticles on their interaction with cells, yet technical difficulties have led to the search for better biomimetics. To overcome such challenges, we aimed to develop a novel method using cell-derived giant plasma membrane vesicles (GPMVs) to encapsulate a variety of engineered nanoparticles, then use these core-shell, nanoparticle-GPMV vesicle structures to deliver cargo to other cells.</p><p><strong>Methods: </strong>GPMVs were generated by chemically inducing vesiculation in A549 cells, a model human alveolar epithelial line. To evaluate the ability of GPMVs to encapsulate intracellular content, plain, carboxy-modified, or amine-modified silica nanoparticles (all, ~ 50 nm diameter) were loaded into the parent cells prior to vesiculation. GPMVs with or without nanoparticles were subsequently evaluated for stability, membrane protein and lipid constituents, and uptake into cells, and compared to relevant controls.</p><p><strong>Results: </strong>Cell-derived GPMVs retained encapsulated silica nanoparticles for at least 48 hours at 37 °C. GPMVs showed nearly identical lipid and protein membrane profiles as the parental cell plasma membrane, with or without encapsulation of nanoparticles. Notably, GPMVs were readily endocytosed in the parental A549 cell line as well as the human monocytic THP-1 cell line. Higher cellular uptake levels were observed for GPMV-encapsulated nanoparticles compared to control groups, including free nanoparticles. Further, GPMVs delivered a variety of nanoparticles to parental cells with reduced cytotoxicity compared to free nanoparticles at concentrations that were otherwise significantly toxic.</p><p><strong>Conclusions: </strong>We have introduced a novel technique to load nanoparticles within the cell plasma membrane during the GPMV vesiculation process. These GPMVs are capable of (a) encapsulating different types of nanoparticles (including larger and not highly-positively charged bodies that have been technically challenging cargoes) using a parental cell uptake technique, and (b) improving delivery of nanoparticles to cells without significant cytotoxicity. Ultimately, the use of GPMVs or other complex vesicles with endogenous cell surface membrane proteins and lipids can lead to highly effective cell membrane-based nanoparticle/drug delivery systems.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"18 3-4","pages":"283-296"},"PeriodicalIF":5.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Actin Branching Regulates Cell Spreading and Force on Talin, but not Activation of YAP.","authors":"Claudia Villalobos, Amir Sadeghifar, Jose Maggiorani, Juliet Delapena, Garrett McDaniel, Tristan P Driscoll","doi":"10.1007/s12195-025-00852-3","DOIUrl":"10.1007/s12195-025-00852-3","url":null,"abstract":"<p><strong>Purpose: </strong>Cells sense the mechanical properties of their environment through physical engagement and spreading, with high stiffness driving nuclear translocation of the mechanosensitive transcription factor YAP. Restriction of cell spread area or environmental stiffness both inhibit YAP activation and nuclear translocation. The Arp2/3 complex plays a critical role in polymerization of branched actin networks that drive cell spreading, protrusion, and migration. While YAP activation has been closely linked to cellular spreading, the specific role of actin branching in force buildup and YAP activation is unclear.</p><p><strong>Methods: </strong>To assess the role of actin branching in this process, we measured cell spreading, YAP nuclear translocation, force on the adhesion adaptor protein Talin (FRET tension sensor), and extracellular forces (traction force microscopy, TFM) in 3T3 cells with and without inhibition of actin branching.</p><p><strong>Results: </strong>The results indicate that YAP activation still occurs when actin branching and cell spreading is reduced. Interestingly, while actin de-branching resulted in decreased force on talin, relatively little change in average traction stress was observed, highlighting the distinct difference between molecular level and cellular level force regulation of YAP.</p><p><strong>Conclusions: </strong>While cell spreading is a driver of YAP nuclear translocation, this is likely through indirect effects. Changes in cell spreading induced by actin branching inhibition do not significantly perturb YAP activation. Additionally, this work provides evidence that focal adhesion molecular forces are not a direct regulator of YAP activation.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-025-00852-3.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"18 3-4","pages":"271-282"},"PeriodicalIF":5.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electric Field-Based Tissue Dissociation: A Paradigm Shift Toward Scalable, Enzyme-Free Single-Cell Preparation.","authors":"Brijesh Sathian, Javed Iqbal, Syed Muhammad Ali","doi":"10.1007/s12195-025-00855-0","DOIUrl":"https://doi.org/10.1007/s12195-025-00855-0","url":null,"abstract":"","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"18 3-4","pages":"211-212"},"PeriodicalIF":5.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative Method for Fully Automated, Enzyme-Free Tissue Dissociation and Preparation for Single-Cell Analysis.","authors":"Sarah Planchak, E Celeste Welch, Benjamin Phelps, Joshua Phelps, Alejandra Hernandez Moyers, Kathryn Whitehead, John Murphy, Nikos Tapinos, Anubhav Tripathi","doi":"10.1007/s12195-025-00850-5","DOIUrl":"https://doi.org/10.1007/s12195-025-00850-5","url":null,"abstract":"<p><strong>Purpose: </strong>Tissue dissociation is a critical but often overlooked step in single-cell analysis, impacting data quality, reproducibility, and biological insights. Conventional enzymatic and mechanical dissociation methods introduce variability, damage cells, and alter transcriptomic profiles, compromising downstream applications. While the initial innovation in electrical dissociation was published, this work introduces expanded characterization, including bulk RNA sequencing, diverse tissue types, and improved flow cytometry.</p><p><strong>Methods: </strong>Here, we present a fully automated, enzyme-free method that integrates electric field-based dissociation with purification and centrifugation, providing a standardized, scalable alternative. A square wave oscillating electric field at 100 V/cm was used for dissociating tissue samples in 5 minutes or less.</p><p><strong>Results: </strong>The system rapidly and gently dissociated glioblastoma spheroids and mouse spleen tissue, achieving a 10 × increase in live cell yield compared to automated enzymatic and mechanical dissociation (gentleMACS) and a 96 ± 2% single-cell recovery rate in glioblastoma spheroids. Transcriptomic analysis revealed minimal gene expression changes post-dissociation, with an R² value of 0.997 between conditions, indicating high consistency. Flow cytometry confirmed that key immune cell populations (B, T, NK cells) were preserved, with comparable distributions between manual and electrical dissociation.</p><p><strong>Conclusions: </strong>By reducing operator variability, improving scalability, and maintaining cellular integrity, this technology offers a robust solution for high-throughput single-cell applications in diagnostics, drug discovery, and precision medicine.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-025-00850-5.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"18 3-4","pages":"251-269"},"PeriodicalIF":5.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examining the Effects of Quercetin on Phenotypic Characteristics of Human Mesenchymal Stem Cells.","authors":"Thomas Needy, David Heinrichs, Vitali Maldonado, Ryan Michael Porter, Hanna Jensen, C Lowry Barnes, Rebekah Margaret Samsonraj","doi":"10.1007/s12195-025-00849-y","DOIUrl":"10.1007/s12195-025-00849-y","url":null,"abstract":"<p><strong>Introduction: </strong>A significant obstacle to mesenchymal stem cell (MSC) potency and therapeutic utility is in vitro senescence, an irreversible cessation of replication associated with age-related complications. Senolytic drugs, such as quercetin, may be helpful in selectively culling senescent cells while leaving non-senescent cells unaffected, thereby increasing potency of high-passage MSCs.</p><p><strong>Methods: </strong>The phenotypic, genotypic, and immunomodulatory effects of quercetin were assessed using in vitro models. Senescent cells, created through repeated subculturing of MSCs in vitro, and non-senescent cells were treated with 10 μM quercetin, differentiated into osteocytes, adipocytes, and chondrocytes, and analyzed to observe the effect of quercetin.</p><p><strong>Results: </strong>Quercetin was not found to be beneficial to MSC function. It did not exhibit a consistent senolytic effect as evidenced by SAβ-gal and live dead staining, hindered proliferation in the short term in some donors, and lowered the expression of osteogenic markers COL1A1 and ALP. Quercetin treatment did not, however, negatively affect adipogenesis, chondrogenesis, or indoleamine 2,3 dioxygenase secretions.</p><p><strong>Conclusion: </strong>This study contributes insight into the nature of quercetin and its effects on in vitro MSC culture and function.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"18 3-4","pages":"239-250"},"PeriodicalIF":5.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial Cells Stably Infected with Recombinant Kaposi's Sarcoma-Associated Herpesvirus Display Distinct Viscoelastic and Morphological Properties.","authors":"Majahonkhe M Shabangu, Melissa J Blumenthal, Danielle T Sass, Dirk M Lang, Georgia Schafer, Thomas Franz","doi":"10.1007/s12195-025-00848-z","DOIUrl":"https://doi.org/10.1007/s12195-025-00848-z","url":null,"abstract":"<p><strong>Purpose: </strong>Kaposi's sarcoma-associated herpesvirus (KSHV) is a γ-herpesvirus that has a tropism for endothelial cells and leads to the development of Kaposi's sarcoma, especially in people living with HIV. The present study aimed to quantify morphological and mechanical changes in endothelial cells after infection with KSHV to assess their potential as diagnostic and therapeutic markers.</p><p><strong>Methods: </strong>Vascular (HuARLT2) and lymphatic endothelial cells (LEC) were infected with recombinant KSHV (rKSHV) by spinoculation, establishing stable infections (HuARLT2-rKSHV and LEC-rKSHV). Cellular changes were assessed using mitochondria-tracking microrheology and morphometric analysis.</p><p><strong>Results: </strong>rKSHV infection increased cellular deformability, indicated by higher mitochondrial mean squared displacement (MSD) for short lag times. Specifically, MSD at τ = 0.19 s was 49.4% and 42.2% higher in HuARLT2-rKSHV and LEC-rKSHV, respectively, compared to uninfected controls. There were 23.9% and 36.7% decreases in the MSD power law exponents for HuARLT2-rKSHV and LEC-rKSHV, respectively, indicating increased cytosolic viscosity associated with rKSHV infection. Infected cells displayed a marked spindloid phenotype with an increase in aspect ratio (29.7%) and decreases in roundness (26.1%) and circularity (25.7%) in HuARLT2-rKSHV, with similar changes observed in LEC-rKSHV.</p><p><strong>Conclusions: </strong>The quantification of distinct KSHV-induced morpho-mechanical changes in endothelial cells demonstrates the potential of these changes as diagnostic markers and therapeutic targets.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"18 2","pages":"123-135"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}