Cellular and molecular bioengineering最新文献

{"title":"Wireless Devices for Optical Brain Stimulation: A Review of Current Developments for Optogenetic Applications in Freely Moving Mice.","authors":"Patrícia Silva, Luis Jacinto","doi":"10.1007/s12195-024-00832-z","DOIUrl":"10.1007/s12195-024-00832-z","url":null,"abstract":"<p><strong>Purpose: </strong>Optogenetics is an invaluable tool to study brain circuits, but typical systems rely on tethered approaches to deliver light to the brain that hinder natural behavior. With the increasing prevalence of complex behavioral phenotyping in neuroscience experiments, wireless devices for optical stimulation offer great promise to overcome these limitations.</p><p><strong>Methods: </strong>In this work we critically review recent systems engineering and device design approaches to deliver light to the brain with wireless operation for optogenetic experiments.</p><p><strong>Results: </strong>We describe strategies used for wireless control and communication, wireless power transfer, and light delivery to the brain with a focus on device integration for in vivo operation in freely behaving mice.</p><p><strong>Conclusion: </strong>Recent advances in optoelectronic systems, material science, and microtechnology have enabled the design and realization of miniaturized wirelessly-controlled optical stimulators for true untethered experiments in rodent models.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"18 1","pages":"1-13"},"PeriodicalIF":2.3,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11813840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413573","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":"A Multicellular Mechanochemical Model to Investigate Tumor Microenvironment Remodeling and Pre-Metastatic Niche Formation.","authors":"Shreyas U Hirway, Kylie G Nairon, Aleksander Skardal, Seth H Weinberg","doi":"10.1007/s12195-024-00831-0","DOIUrl":"10.1007/s12195-024-00831-0","url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal cancer (CRC) is a major cause of cancer related deaths in the United States, with CRC metastasis to the liver being a common occurrence. The development of an optimal metastatic environment is essential process prior to tumor metastasis. This process, called pre-metastatic niche (PMN) formation, involves activation of key resident liver cells, including fibroblast-like stellate cells and macrophages such as Kupffer cells. Tumor-mediated factors introduced to this environment transform resident cells that secrete additional growth factors and remodel the extracellular matrix (ECM), which is thought to promote tumor colonization and metastasis in the secondary environment.</p><p><strong>Methods: </strong>To investigate the underlying mechanisms of these dynamics, we developed a multicellular computational model to characterize the spatiotemporal dynamics of the PMN formation in tissue. This modeling framework integrates intracellular and extracellular signaling, and traction and junctional forces into a Cellular Potts model, and represents multiple cell types with varying levels of cellular activation. We perform numerical experiments to investigate the role of key factors in PMN formation and tumor invasiveness, including growth factor concentration, timing of tumor arrival, relative composition of resident cells, and the size of invading tumor cluster.</p><p><strong>Results: </strong>These parameter studies identified growth factor availability and ECM concentration in the environment as two of the key determinants of tumor invasiveness. We further predict that both the ECM concentration potential and growth factor sensitivity of the stellate cells are key drivers of the PMN formation and associated ECM concentration.</p><p><strong>Conclusions: </strong>Overall, this modeling framework represents a significant step towards simulating cancer metastasis and investigating the role of key factors on PMN formation.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-024-00831-0.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"17 6","pages":"573-596"},"PeriodicalIF":2.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381703","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":"Assessing the Effects of Dasatinib on Mesenchymal Stem/Stromal Cells.","authors":"David P Heinrichs, Vitali V Maldonado, I Kade K Ardana, Ryan M Porter, Rebekah M Samsonraj","doi":"10.1007/s12195-024-00830-1","DOIUrl":"10.1007/s12195-024-00830-1","url":null,"abstract":"<p><strong>Introduction: </strong>Progressive aging, or senescence, of mesenchymal stem/stromal cells (MSCs) is a major obstacle faced when trying to culture potent stem cells for use in therapy. Senescent cells are irreversibly nondividing cells that cease performing critical functional effects. Elimination of senescent cells using biochemical means, such as the use of senolytic drugs like dasatinib, may be useful in retaining the viable and proliferating populations of the cells.</p><p><strong>Methods: </strong>An in vitro approach was used to investigate the effect of dasatinib on phenotypic, genotypic, and immunomodulatory functionality of osteogenic and adipogenic differentiated MSCs. Replicative senescence was achieved through multiple sub-culturing in vitro, then senescent and non-senescent cultures were treated with a standard dosage of dasatinib. MSCs were then differentiated into osteogenic, adipogenic or chondrogenic cultures using conditioned media to be tested for the three criteria being investigated.</p><p><strong>Results: </strong>Significant changes were observed in these criteria, indicated by evidence gathered from proliferation and indoleamine 2,3 dioxygenase activity assays. Phenotypic results of dasatinib were shown to reduce the population of senescent MSCs while allowing non-senescent MSCs to continue differentiating and proliferating without interference from senescent cells. Genotypic results showed no change to upregulation in markers associated with osteogenic and adipogenic cells when exposed to dasatinib. Indoleamine Dioxygenase activity showed insignificant differences in cells exposed to dasatinib versus control groups, providing evidence against compromised cellular immune function.</p><p><strong>Conclusion: </strong>This investigation provides insight into how dasatinib effects MSCs functional ability and provides a better understanding of the function of senolytic agents.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"17 6","pages":"609-618"},"PeriodicalIF":2.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381617","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":"Fibroblast-Adipocyte Lineage Cell Interactions Result in Differential Production of Extracellular Matrix Proteins.","authors":"Edward A Sander, Mariam Y El-Hattab, Kathryn R Jacobson, Aloysius J Klingelhutz, James A Ankrum, Sarah Calve","doi":"10.1007/s12195-024-00829-8","DOIUrl":"10.1007/s12195-024-00829-8","url":null,"abstract":"<p><strong>Introduction: </strong>Scarring from traumatic injury, burns, and other complications remains a significant problem that diminishes quality of life for millions of people worldwide. A common target for the development of new therapies to promote healing and reduce scarring are myofibroblasts because of their central role in pathological scarring. Recent work indicates that adipocyte lineage cells also contribute to the wound healing process, including clinical reports that indicate that the placement of autologous adipose micrografts at the surgical site improves the appearance and pliability of existing scars.</p><p><strong>Methods: </strong>To better understand how adipocyte lineage cells interact with fibroblasts to promote healing, we first utilized an <i>in vitro</i> model of wound healing to visualize fibroblast spheroid collagen deposition via time-lapse imaging. We then introduced pre-adipocyte and adipocyte spheroids to visualize pair-wise spheroid interactions and collagen deposition among all three cell types. Finally, we quantified differences in the extracellular matrix (ECM) proteins produced using liquid chromatography with tandem mass spectrometry (LC-MS/MS).</p><p><strong>Results: </strong>We found that all three cell-types contribute to ECM deposition and that the composition of the ECM proteins, or matrisome, was significantly different depending on which cells were co-cultured together.</p><p><strong>Conclusions: </strong>By better understanding the interactions among these cell types, novel adipose-tissue-based therapeutic approaches can be developed to improve wound healing and reduce scar tissue.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-024-00829-8.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"17 6","pages":"597-608"},"PeriodicalIF":2.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381621","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":"Remote-Controlled Gene Delivery in Coaxial 3D-Bioprinted Constructs using Ultrasound-Responsive Bioinks.","authors":"Mary K Lowrey, Holly Day, Kevin J Schilling, Katherine T Huynh, Cristiane M Franca, Carolyn E Schutt","doi":"10.1007/s12195-024-00818-x","DOIUrl":"https://doi.org/10.1007/s12195-024-00818-x","url":null,"abstract":"<p><strong>Introduction: </strong>Coaxial 3D bioprinting has advanced the formation of tissue constructs that recapitulate key architectures and biophysical parameters for in-vitro disease modeling and tissue-engineered therapies. Controlling gene expression within these structures is critical for modulating cell signaling and probing cell behavior. However, current transfection strategies are limited in spatiotemporal control because dense 3D scaffolds hinder diffusion of traditional vectors. To address this, we developed a coaxial extrusion 3D bioprinting technique using ultrasound-responsive gene delivery bioinks. These bioink materials incorporate echogenic microbubble gene delivery particles that upon ultrasound exposure can sonoporate cells within the construct, facilitating controllable transfection.</p><p><strong>Methods: </strong>Phospholipid-coated gas-core microbubbles were electrostatically coupled to reporter transgene plasmid payloads and incorporated into cell-laden alginate bioinks at varying particle concentrations. These bioinks were loaded into the coaxial nozzle core for extrusion bioprinting with CaCl₂ crosslinker in the outer sheath. Resulting bioprints were exposed to 2.25 MHz focused ultrasound and evaluated for microbubble activation and subsequent DNA delivery and transgene expression.</p><p><strong>Results: </strong>Coaxial printing parameters were established that preserved the stability of ultrasound-responsive gene delivery particles for at least 48 h in bioprinted alginate filaments while maintaining high cell viability. Successful sonoporation of embedded cells resulted in DNA delivery and robust ultrasound-controlled transgene expression. The number of transfected cells was modulated by varying the number of focused ultrasound pulses applied. The size region over which DNA was delivered was modulated by varying the concentration of microbubbles in the printed filaments.</p><p><strong>Conclusions: </strong>Our results present a successful coaxial 3D bioprinting technique designed to facilitate ultrasound-controlled gene delivery. This platform enables remote, spatiotemporally-defined genetic manipulation in coaxially bioprinted tissue constructs with important applications for disease modeling and regenerative medicine.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-024-00818-x.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"17 5","pages":"401-421"},"PeriodicalIF":2.3,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602127","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":"Mechanical Trapping of the Cell Nucleus Into Microgroove Concavity But Not On Convexity Induces Cell Tissue Growth and Vascular Smooth Muscle Differentiation.","authors":"Kazuaki Nagayama, Naoki Wataya","doi":"10.1007/s12195-024-00827-w","DOIUrl":"10.1007/s12195-024-00827-w","url":null,"abstract":"<p><strong>Introduction: </strong>Vascular smooth muscle cells (VSMCs) in the normal aortic wall regulate vascular contraction and dilation. VSMCs change their phenotype from contractile to synthetic and actively remodel the aortic wall under pathological conditions. Findings on the differentiation mechanism of VSMCs have been reported in many in vitro studies; however, the mechanical environments in vivo aortic walls are quite different from those of in vitro culture conditions: VSMCs in vivo exhibit an elongated shape and form a tissue that aligns with the circumferential direction of the walls, whereas VSMCs in vitro spread randomly and form irregular shapes during cultivation on conventional flat culture dishes and dedifferentiate into a synthetic phenotype. To clarify the mechanisms underlying the VSMC differentiation, it is essential to develop a cell culture model that considers the mechanical environment of in vivo aortic walls.</p><p><strong>Methods: </strong>We fabricated a polydimethylsiloxane-based microgrooved substrate with 5, 10, and 20 μm of groove width and 5 μm of groove depth to induce VSMC elongation and alignment as observed in vivo. We established a coating method to control cell adhesion proteins only on the surface of groove concavities and investigated the effects of mechanical trapping of the cell nucleus in microgroove concavities on the morphology of intracellular nuclei, cell proliferation and motility, and VSMC differentiation.</p><p><strong>Results: </strong>We found that VSMCs adhering to the concavities formed a uniform cell tissue and allowed remarkable elongation. In particular, the microgrooves with 5 μm of groove width and depth facilitated a significant nuclear deformation and volume reduction of the nucleus due to a lateral compression by the side wall of the groove concavities that is relatively similar to a sandwich-like arrangement of in vivo elastic lamellae, resulting in the drastic inhibition of cell motility and proliferation, and the significant improvement of VSMC differentiation.</p><p><strong>Conclusions: </strong>The results indicate that mechanical trapping of the cell nucleus into microgroove concavity but not on convexity induces cell tissue growth and VSMC differentiation. Our cell culture model with microgrooved substrates can be useful for studying the mechanisms of VSMC differentiation, considering the in vivo vascular mechanical environment.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-024-00827-w.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"17 6","pages":"549-562"},"PeriodicalIF":2.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381623","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":"Simulation of Somatic Evolution Through the Introduction of Random Mutation to the Rules of Conway's Game of Life.","authors":"Michael R King","doi":"10.1007/s12195-024-00828-9","DOIUrl":"10.1007/s12195-024-00828-9","url":null,"abstract":"<p><strong>Introduction: </strong>Conway's Game of Life (GOL), and related cellular automata (CA) models, have served as interesting simulations of complex behaviors resulting from simple rules of interactions between neighboring cells, that sometime resemble the growth and reproduction of living things. Thus, CA has been applied towards understanding the interaction and reproduction of single-cell organisms, and the growth of larger, disorganized tissues such as tumors. Surprisingly, however, there have been few attempts to adapt simple CA models to recreate the evolution of either new species, or subclones within a multicellular, tumor-like tissue.</p><p><strong>Methods: </strong>In this article, I present a modified form of the classic Conway's GOL simulation, in which the three integer thresholds that define GOL (number of neighboring cells, below which a cell will \"die of loneliness\"; number of neighboring cells, above which a cell will die of overcrowding; and number of neighboring cells that will result in spontaneous birth of a new cell within an empty lattice location) are occasionally altered with a randomized mutation of fractional magnitude during new \"cell birth\" events. Newly born cells \"inherit\" the current mutation state of a neighboring parent cell, and over the course of 10,000 generations these mutations tend to accumulate until they impact the behaviors of individual cells, causing them to transition from the sparse, small patterns of live cells characteristic of GOL into a more dense, unregulated growth resembling a connected tumor tissue.</p><p><strong>Results: </strong>The mutation rate and mutation magnitude were systematically varied in repeated randomized simulation runs, and it was determined that the most important mutated rule for the transition to unregulated, tumor-like growth was the overcrowding threshold, with the spontaneous birth and loneliness thresholds being of secondary importance. Spatial maps of the different \"subclones\" of cells that spontaneously develop during a typical simulation trial reveal that cells with greater fitness will overgrow the lattice and proliferate while the less fit, \"wildtype\" GOL cells die out and are replaced with mutant cells.</p><p><strong>Conclusions: </strong>This simple modeling approach can be easily modified to add complexity and more realistic biological details, and may yield new understanding of cancer and somatic evolution.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-024-00828-9.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"17 6","pages":"563-571"},"PeriodicalIF":2.3,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381628","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":"Organoids as Sophisticated Tools for Renal Cancer Research: Extensive Applications and Promising Prospects.","authors":"Jingqiang Huang, Xianli Wang, Shengyang Ge, Xiao Lu, Chuanyu Sun","doi":"10.1007/s12195-024-00825-y","DOIUrl":"10.1007/s12195-024-00825-y","url":null,"abstract":"<p><strong>Background: </strong>Kidney cancer is a significant global health problem that affects nearly 1 in 25 of cancer patients. Prevalence, morbidity and mortality data associated with kidney cancer continue to increase every year, revealing a heavy economic and social burden. Organoid culture is a new research tool with great potential for many applications, particularly in cancer research. The integration of organoids with other emerging technologies has simultaneously expanded their potential applications. However, there is no thorough assessment of organoids in the field of renal cancer research.</p><p><strong>Objectives: </strong>This paper presents a comprehensive review of the current development of renal cancer organoids and discusses the corresponding solutions and future directions of renal cancer organoids.</p><p><strong>Methods: </strong>In this study, we have compared the operating procedures of different organoid culture protocols and proposed a summary of constituents in culture media. Extensive discussions of renal cancer organoids, including generation and maintenance approaches, application scenarios, current challenges and prospects, have also been made. The information required for this study is extracted from literature databases such as PubMed, SCOPUS and Web of Science.</p><p><strong>Results: </strong>In this article, we systematically review thirteen successful methods for generating organoids to kidney cancer and provide practical guidelines for their construction as a reference. In addition, we also elucidate the clinical application of organoids, address the existing challenges and limitations, and highlight promising prospects.</p><p><strong>Conclusion: </strong>Ultimately, we firmly believe that as kidney tumour organoids continue to develop and improve, they will become a crucial tool for treating kidney cancer.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"17 6","pages":"527-548"},"PeriodicalIF":2.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381625","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":"The 2024 Young Innovators of Cellular and Molecular Bioengineering.","authors":"Michael R King, Robert M Raphael, Joyce Y Wong","doi":"10.1007/s12195-024-00826-x","DOIUrl":"https://doi.org/10.1007/s12195-024-00826-x","url":null,"abstract":"","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"17 5","pages":"313-315"},"PeriodicalIF":2.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602164","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":"Novel 3-D Macrophage Spheroid Model Reveals Reciprocal Regulation of Immunomechanical Stress and Mechano-Immunological Response.","authors":"Alice Burchett, Saeed Siri, Jun Li, Xin Lu, Meenal Datta","doi":"10.1007/s12195-024-00824-z","DOIUrl":"10.1007/s12195-024-00824-z","url":null,"abstract":"<p><strong>Purpose: </strong>In many diseases, an overabundance of macrophages contributes to adverse outcomes. While numerous studies have compared macrophage phenotype after mechanical stimulation or with varying local stiffness, it is unclear if and how macrophages directly contribute to mechanical forces in their microenvironment.</p><p><strong>Methods: </strong>Raw 264.7 murine macrophages were embedded in a confining agarose gel, and proliferated to form spheroids over days/weeks. Gels were synthesized at various concentrations to tune stiffness and were shown to support cell viability and spheroid growth. These cell-agarose constructs were treated with media supplements to promote macrophage polarization. Spheroid geometries were used to computationally model the strain generated in the agarose by macrophage spheroid growth. Agarose-embedded macrophages were analyzed for viability, spheroid size, stress generation, and gene expression.</p><p><strong>Results: </strong>Macrophages form spheroids and generate growth-induced mechanical forces (i.e., solid stress) within confining agarose gels, which can be maintained for at least 16 days in culture. Increasing agarose concentration increases gel stiffness, restricts spheroid expansion, limits gel deformation, and causes a decrease in Ki67 expression. Lipopolysaccharide (LPS) stimulation increases spheroid growth, though this effect is reversed with the addition of IFNγ. The mechanosensitive ion channels Piezo1 and TRPV4 have reduced expression with increased stiffness, externally applied compression, LPS stimulation, and M1-like polarization.</p><p><strong>Conclusions: </strong>Macrophages alone both respond to and generate solid stress. Understanding how macrophage generation of growth-induced solid stress responds to different environmental conditions will help to inform treatment strategies for the plethora of diseases that involve macrophage accumulation and inflammation.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-024-00824-z.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"17 5","pages":"329-344"},"PeriodicalIF":4.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603396","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}