Kamila Kolanska, Merwane Roche, Camille Carrière, Marjolaine Le Gac, Nathalie Ferrand, Maurice Zaoui, Morgane Le Gall, Lise Selleret, Joseph Gligorov, Michèle Sabbah, Selim Aractingi, Nathalie Chabbert-Buffet
{"title":"Impact of Fetal Umbilical Cord Blood CD34+ Cells on Breast Cancer Cell Lines: A Mechanism of Fetal Microchimerism.","authors":"Kamila Kolanska, Merwane Roche, Camille Carrière, Marjolaine Le Gac, Nathalie Ferrand, Maurice Zaoui, Morgane Le Gall, Lise Selleret, Joseph Gligorov, Michèle Sabbah, Selim Aractingi, Nathalie Chabbert-Buffet","doi":"10.1159/000542242","DOIUrl":"10.1159/000542242","url":null,"abstract":"<p><strong>Introduction: </strong>Fetal microchimerism could be involved in the regulation of breast cancer oncogenesis. CD34+ cells could be of a particular interest as up to 12% of the CD34+ population in maternal blood are of fetal origin. The aim of this research was to analyze the impact of umbilical cord blood (UCB) CD34+ on MCF-7 and MDA-MB-231 breast cancer cell lines, in order to uncover novel biological mechanisms and suggest novel treatment options for breast cancer.</p><p><strong>Methods: </strong>UCB CD34+ cells were obtained from healthy women at full-term delivery. Direct cultures were grown with MCF-7 and MDA-MB-231 cells. Proliferation, migration, invasion, and transcriptomic analysis of breast cancer cell lines were compared between cultures exposed and nonexposed to UCB CD34+ cells. Interactions between UCB CD34+ and breast cancer cells were analyzed under fluorescent microscopy. Functional analyses were generated with QIAGEN's Ingenuity Pathway Analysis (IPA) and Gene Set Enrichment Analysis (GSEA).</p><p><strong>Results: </strong>Direct contact between UCB CD34+ and breast cancer cell lines induced a reduction in the proliferative capacities of MCF-7 and MDA-MB-231 and diminished the migration abilities of MDA-MB-231 cells. In 3D coculture, UCB CD34+ cells were attracted by tumor spheroids and incorporated into tumor cells. These cell-to-cell interactions were responsible for transcriptome modifications coherent with observed functional modifications. Among the cytokines secreted by UCB CD34+, IFN-γ was identified as a potential upstream regulator responsible for the molecular modifications observed in transcriptomic analysis of MCF-7 breast cancer cells exposed to UCB CD34+ cells, as was IL-17A in MDA-MB-231 cells.</p><p><strong>Conclusion: </strong>Direct cell-to-cell contact induced functional modifications in breast cancer cells. Interactions between UCB CD34+ and breast cancer cells could induce cell fusion and signal transmission via cytokines. Further analysis of direct cell-to-cell interactions should be performed at a molecular level to further understand the potential role of fetal CD34+ cells in breast cancer.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-16"},"PeriodicalIF":2.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dalia Mohamedien, Wafaa Gaber, Makoto Hirayama, Mahmoud Awad
{"title":"Detection of MUC1+/MUC2 and MUC5AC- Membrane-Associated Mucins in the Intraepithelial Surface Mucous Cells of the Developing Rabbit Esophagus.","authors":"Dalia Mohamedien, Wafaa Gaber, Makoto Hirayama, Mahmoud Awad","doi":"10.1159/000541836","DOIUrl":"10.1159/000541836","url":null,"abstract":"<p><strong>Introduction: </strong>Mucins are polydisperse molecules created to perform a variety of functions at the mucosal surface of the adult gastrointestinal tract. Two main groups of mucins could be identified: the membrane-associated mucins (MUC1, MUC4, MUC13, and MUC16), those bound to the apical plasma membrane of epithelial cells, and the secreted mucins (MUC2, MUC5AC, MUC5B, and MUC6), those secreted from the goblet cells. Little is known about the types and distribution patterns of mucins in prenatal life.</p><p><strong>Methods: </strong>We detected mucin-secreting cells in the developing rabbit esophagus though these cells are absent in the adult one. In order to identify the content and possible functions of these cells, we investigated the histochemical and immunohistochemical characteristics of their mucins.</p><p><strong>Results: </strong>Starting at 16th day of pregnancy, periodic acid Schiff (PAS), alcian blue (AB) pH (2.5), and PAS-AB combination intensely stained the mucous content, demonstrating both acidic and neutral mucopolysaccharides. Some blebs could be recognized on the free surface of the esophageal epithelium. Also, the mucous cells and some basal cells strongly immunoreacted with MUC1, but not MUC2, nor MUC5AC antibodies.</p><p><strong>Conclusion: </strong>Collectively, these data suggest that surface mucous cells are modified epithelial cells, not goblet cells, and may originate from the basal layer of the epithelial cells. A possible regulatory role for these MUC1-positive mucins in esophageal epithelial and mesenchymal cell differentiation and late organogenesis is suggested. However, future functional studies are recommended.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-13"},"PeriodicalIF":2.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spheroid-Hydrogel Integrated Biomimetic System (SHIBS): A New Frontier in Advanced 3D Cell Culture Technology.","authors":"Seungyeop Yoo,Hyun Jong Lee","doi":"10.1159/000541416","DOIUrl":"https://doi.org/10.1159/000541416","url":null,"abstract":"BACKGROUNDDespite significant advances in three-dimensional (3D) cell culture technologies, creating accurate in vitro models that faithfully recapitulate complex in vivo environments remains a major challenge in biomedical research. Traditional culture methods often fail to simultaneously facilitate critical cell-cell and cell-extracellular matrix (ECM) interactions while providing control over mechanical and biochemical properties.SUMMARYThis review introduces the spheroid-hydrogel integrated biomimetic system (SHIBS), a groundbreaking approach that synergistically combines spheroid culture with tailored hydrogel technologies. SHIBS uniquely bridges the gap between traditional culture methods and physiological conditions by offering unprecedented control over both cellular interactions and environmental properties. We explore how SHIBS is revolutionizing fields ranging from drug discovery and disease modeling to regenerative medicine and basic biological research. The review discusses current challenges in SHIBS technology, including reproducibility, scalability, and high-resolution imaging, and outlines ongoing research addressing these issues. Furthermore, we envision the future evolution of SHIBS into more sophisticated organoid-hydrogel integrated biomimetic systems (OHIBS) and its integration with cutting-edge technologies such as microfluidics, 3D bioprinting, and artificial intelligence.KEY MESSAGESSHIBS represents a paradigm shift in 3D cell culture technology, offering a unique solution to recreate complex in vivo environments. Its potential to accelerate the development of personalized therapies across various biomedical fields is significant. While challenges persist, the ongoing advancements in SHIBS technology promise to overcome current limitations, paving the way for more accurate and reliable in vitro models. The future integration of SHIBS with emerging technologies may revolutionize biomimetic modeling, potentially reducing the need for animal testing and expediting drug discovery processes. This comprehensive review provides researchers and clinicians with a holistic understanding of SHIBS technology, its current capabilities, and its future prospects in advancing biomedical research and therapeutic innovations.","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":"10 1","pages":"1-30"},"PeriodicalIF":2.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Three-Dimensional Imaging Analysis of the Developmental Process of Posterior Meniscofemoral Ligaments in Rat Embryos.","authors":"Momoko Nagai-Tanima, Kanon Ishida, Aoi Ishikawa, Shigehito Yamada, Tetsuya Takakuwa, Tomoki Aoyama","doi":"10.1159/000536108","DOIUrl":"10.1159/000536108","url":null,"abstract":"<p><strong>Introduction: </strong>The posterior meniscofemoral ligament (pMFL) of knee joint is a ligament that runs posterior to the posterior cruciate ligament and it is known that the height of the pMFL attachment site causes meniscus avulsion. Therefore, understanding the three-dimensional (3D) structure of the pMFL attachment site is essential to better understand the pathogenesis of meniscus disorders. However, the developmental process of pMFL has not been well investigated. The purpose of this study was to analyze pMFL development in rat knee joints using 3D reconstructed images produced from episcopic fluorescence image capture (EFIC) images and examine its relationship with other knee joint components.</p><p><strong>Methods: </strong>Knee joints of Wistar rat embryos between embryonic day (E) 16 and E21 were observed with HE-stained tissues. Serial EFIC images of the hind limbs of E17-E21 were, respectively, captured from which 3D images were reconstructed and the features of pMFL structure: length and angle were measured. Besides, the chronological volume changes and the volume ratio of the knee joint components compared to E17 were calculated to identify the differences in growth by components.</p><p><strong>Results: </strong>pMFL was observed from E17 and was attached to the medial femoral condyle and lateral meniscus at all developmental stages, as in mature rats. The lack of marked variation in the attachment site and angle of the pMFL with the developmental stage indicates that the pMFL and surrounding knee joint components developed while maintaining their positional relationship from the onset of development.</p><p><strong>Conclusion: </strong>Current results may support to congenital etiology of meniscus disorder.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"357-367"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377248","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}
Cells Tissues OrgansPub Date : 2024-01-01Epub Date: 2024-01-09DOI: 10.1159/000536096
Pierre Savagner, Thomas Brabletz, Chonghui Cheng, Christine Gilles, Tian Hong, Myriam Polette, Guojun Sheng, Marc P Stemmler, Erik W Thompson
{"title":"Twenty Years of Epithelial-Mesenchymal Transition: A State of the Field from TEMTIA X.","authors":"Pierre Savagner, Thomas Brabletz, Chonghui Cheng, Christine Gilles, Tian Hong, Myriam Polette, Guojun Sheng, Marc P Stemmler, Erik W Thompson","doi":"10.1159/000536096","DOIUrl":"10.1159/000536096","url":null,"abstract":"<p><p>This report summarizes the 10th biennial meeting of The Epithelial Mesenchymal Transition International Association (TEMTIA), that took place in Paris on November 7-10, 2022. It provides a short but comprehensive introduction to the presentations and discussions that took place during the 3-day meeting. Similarly to previous TEMTIA meetings, TEMTIA X reviewed the most recent aspects of the epithelial-mesenchymal transition (EMT), a cellular process involved during distinct stages of development but also during wound healing and fibrosis to some degree. EMT has also been associated at various levels during tumor cell progression and metastasis. The meeting emphasized the intermediate stages of EMT (partial EMT or EM hybrid cells) involved in the malignant process and their potential physiological or pathological importance, taking advantage of advancements in molecular methods at the single-cell level. It also introduced novel descriptions of EMT occurrences during early embryogenesis. Sessions explored relationships between EMT and cell metabolism and how EMT can affect immune responses, particularly during tumor progression, providing new targets for cancer therapy. Finally, it introduced a new perception of EMT biological meaning based on an evolutionary perspective. The meeting integrated the TEMTIA general assembly, allowing general discussion about the future of the association and the site of the next meeting, now decided to take place in Seattle, USA, in November 2024. This report provides a comprehensive introduction to the presentations and discussions that took place during the 10th biennial meeting of TEMTIA, that occurred in Paris on November 7-10, 2022. It includes all the sessions and follows the chronological order during the 3-day meeting. A general purpose of the meeting was to explore the boundaries of the EMT process, including new concepts and developments, as illustrated by our leitmotiv for the meeting, inspired by the proximity of the Cluny Museum in Paris.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"297-303"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cells Tissues OrgansPub Date : 2024-01-01Epub Date: 2023-05-22DOI: 10.1159/000531098
Michael M Sutton, Michael P Duffy, Stefaan W Verbruggen, Christopher R Jacobs
{"title":"Osteoclastogenesis Requires Primary Cilia Disassembly and Can Be Inhibited by Promoting Primary Cilia Formation Pharmacologically.","authors":"Michael M Sutton, Michael P Duffy, Stefaan W Verbruggen, Christopher R Jacobs","doi":"10.1159/000531098","DOIUrl":"10.1159/000531098","url":null,"abstract":"<p><p>The primary cilium is a solitary, sensory organelle with many roles in bone development, maintenance, and function. In the osteogenic cell lineage, including skeletal stem cells, osteoblasts, and osteocytes, the primary cilium plays a vital role in the regulation of bone formation, and this has made it a promising pharmaceutical target to maintain bone health. While the role of the primary cilium in the osteogenic cell lineage has been increasingly characterized, little is known about the potential impact of targeting the cilium in relation to osteoclasts, a hematopoietic cell responsible for bone resorption. The objective of this study was to determine whether osteoclasts have a primary cilium and to investigate whether or not the primary cilium of macrophages, osteoclast precursors, serves a functional role in osteoclast formation. Using immunocytochemistry, we showed the macrophages have a primary cilium, while osteoclasts lack this organelle. Furthermore, we increased macrophage primary cilia incidence and length using fenoldopam mesylate and found that cells undergoing such treatment showed a significant decrease in the expression of osteoclast markers tartrate-resistant acid phosphatase, cathepsin K, and c-Fos, as well as decreased osteoclast formation. This work is the first to show that macrophage primary cilia resorption may be a necessary step for osteoclast differentiation. Since primary cilia and preosteoclasts are responsive to fluid flow, we applied fluid flow at magnitudes present in the bone marrow to differentiating cells and found that osteoclastic gene expression by macrophages was not affected by fluid flow mechanical stimulation, suggesting that the role of the primary cilium in osteoclastogenesis is not a mechanosensory one. The primary cilium has been suggested to play a role in bone formation, and our findings indicate that it may also present a means to regulate bone resorption, presenting a dual benefit of developing ciliary-targeted pharmaceuticals for bone disease.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"235-244"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10863750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9876677","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}
Cells Tissues OrgansPub Date : 2024-01-01Epub Date: 2023-10-30DOI: 10.1159/000534892
Fuka Takeuchi, Aki Sugano, Azusa Yoneshige, Man Hagiyama, Takao Inoue, Akihiro Wada, Yutaka Takaoka, Akihiko Ito
{"title":"Potential Contribution of Cell Adhesion Molecule 1 to the Binding of SARS-CoV-2 Spike Protein to Mouse Nasal Mucosa.","authors":"Fuka Takeuchi, Aki Sugano, Azusa Yoneshige, Man Hagiyama, Takao Inoue, Akihiro Wada, Yutaka Takaoka, Akihiko Ito","doi":"10.1159/000534892","DOIUrl":"10.1159/000534892","url":null,"abstract":"<p><p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first infects the host nasal mucosa, where the viral spike protein binds to angiotensin-converting enzyme 2 (ACE2) on the mucosal cells. This study aimed at searching host cell surface molecules that could contribute to the infection in two views; abundance on host cells and affinity to the spike protein. Since the nasal mucosa is lined by respiratory and olfactory epithelia, and both express an immunoglobulin superfamily member cell adhesion molecule 1 (CADM1), whether CADM1 would participate in the spike protein binding was examined. Immunohistochemistry on the mouse nasal cavity detected CADM1 strongly in the olfactory epithelium at cell-cell contacts and on the apical surface but just faintly in the respiratory epithelium. In contrast, ACE2 was detected in the respiratory, not olfactory, epithelium. When mice were administered intranasally with SARS-CoV-2 S1 spike protein and an anti-CADM1 ectodomain antibody separately, both were detected exclusively on the olfactory, not respiratory, epithelium. Then, the antibody and S1 spike protein were administered intranasally to mice in this order with an interval of 1 h. After 3 h, S1 spike protein was detected as a protein aggregate floating in the nasal cavity. Next, S1 spike protein labeled with fluorescein was added to the monolayer cultures of epithelial cells exogenously expressing ACE2 or CADM1. Quantitative detection of fluorescein bound to the cells revealed that S1 spike protein bound to CADM1 with affinity half as high as to ACE2. Consistently, docking simulation analyses revealed that S1 spike protein could bind to CADM1 three-quarters as strongly as to ACE2 and that the interface of ACE2 was similar in both binding modes. Collectively, intranasal S1 spike protein appeared to prefer to accumulate on the olfactory epithelium, and CADM1 was suggested to contribute to this preference of S1 spike protein based on the molecular abundance and affinity.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"326-337"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71410902","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}
Cells Tissues OrgansPub Date : 2024-01-01Epub Date: 2023-11-09DOI: 10.1159/000535018
Nur Hidayah Hassan, Raja Elina Ahmad, Tunku Kamarul, Qi Hao Daniel Looi, Pan Pan Chong
{"title":"Allogenic Platelet-Rich Plasma for Treating Cartilage Injury: A Systematic Review of the Evidence on the Basic Sciences for Potential Future Applications.","authors":"Nur Hidayah Hassan, Raja Elina Ahmad, Tunku Kamarul, Qi Hao Daniel Looi, Pan Pan Chong","doi":"10.1159/000535018","DOIUrl":"10.1159/000535018","url":null,"abstract":"<p><p>It is apparent that whilst many reports are available regarding platelet-rich-plasma (PRP), the larger majority of these have been mainly focussed on autologous sources, and for good reason. Issues relating to allogenic source have been consciously avoided owing to concerns of cross infectivity and immune rejection. However, this topic today is now revisited and is of interest since progress over the year has demonstrated its safety, efficacy, and its abundance of supply. The present systematic review was thus conducted to elucidate advances made in this area, with the aim to provide a wider and deeper understanding of studies relevant to the application of allogenic PRP in cartilage repair. Literature search was conducted systematically using Medline, ProQuest, Web of Science, Cochrane Central Register of Controlled Trials, and snowballing searching strategy to identify relevant studies using topic-specific keywords in various combinations including \"allogenic, platelet, rich, plasma\" OR \"allogeneic, platelet, rich, plasma\" OR \"allogenic platelet-rich plasma\" OR \"allogeneic platelet-rich plasma\" OR \"allogenic platelet rich plasma\" OR \"allogeneic platelet rich plasma\" AND cartilage OR chondrocytes OR synoviocytes OR stem cells. Studies that used allogenic PRP in an attempt to facilitate cartilage repair were included. The risk of bias was assessed by the SYRCLE's checklist. Of 206 studies identified, 12 were found eligible. Only those studies that are clearly related and specific to allogenic PRP were included. Of these, nine investigated the efficacy of allogenic PRP in animal models, while three articles employed an in vitro model. Allogenic PRP promotes cell proliferation, cartilage matrix production, and anti-inflammatory effects in vitro. The in vivo studies reported histological evidence of significant acceleration of cartilage repair in treated animals. Despite several conflicting findings, all studies agreed that allogenic PRP is safe and potentially efficacious for cartilage repair, with the advantages of allogenic sources apparent.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"338-355"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72013634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cells Tissues OrgansPub Date : 2024-01-01Epub Date: 2024-05-20DOI: 10.1159/000539319
Vaishali Bala, Vidhi Patel, Mary Kathryn Sewell-Loftin
{"title":"Cadherin Expression Is Regulated by Mechanical Phenotypes of Fibroblasts in the Perivascular Matrix.","authors":"Vaishali Bala, Vidhi Patel, Mary Kathryn Sewell-Loftin","doi":"10.1159/000539319","DOIUrl":"10.1159/000539319","url":null,"abstract":"<p><strong>Introduction: </strong>The influence of mechanical forces generated by stromal cells in the perivascular matrix is thought to be a key regulator in controlling blood vessel growth. Cadherins are mechanosensors that facilitate and maintain cell-cell interactions and blood vessel integrity, but little is known about how stromal cells regulate cadherin signaling in the vasculature. Our objective was to investigate the relationship between mechanical phenotypes of stromal cells with cadherin expression in 3D tissue engineering models of vascular growth.</p><p><strong>Methods: </strong>Stromal cell lines were subjected to a bead displacement assay to track matrix distortions and characterize mechanical phenotypes in 3D microtissue models. These cells included human ventricular cardiac (NHCF), dermal (NHDF), lung (NHLF), breast cancer-associated (CAF), and normal breast fibroblasts (NBF). Cells were embedded in a fibrin matrix (10 mg/mL) with fluorescent tracker beads; images were collected every 30 min. We also studied endothelial cells (ECs) in co-culture with mechanically active or inactive stromal cells and quantified N-Cad, OB-Cad, and VE-Cad expression using immunofluorescence.</p><p><strong>Results: </strong>Bead displacement studies identified mechanically active stromal cells (CAFs, NHCFs, NHDFs) that generate matrix distortions and mechanically inactive cells (NHLFs, NBFs). CAFs, NHCFs, and NHDFs displaced the matrix with an average magnitude of 3.17 ± 0.11 μm, 3.13 ± 0.06 μm, and 2.76 ± 0.05 μm, respectively, while NHLFs and NBFs displaced the matrix with an average of 1.82 ± 0.05 μm and 2.66 ± 0.06 μm in fibrin gels. Compared to ECs only, CAFs + ECs as well as NBFs + ECs in 3D co-culture significantly decreased expression of VE-Cad; in addition, Pearson's Correlation Coefficient for N-Cad and VE-Cad showed a strong correlation (>0.7), suggesting cadherin colocalization. Using a microtissue model, we demonstrated that mechanical phenotypes associated with increased matrix deformations correspond to enhanced angiogenic growth. The results could suggest a mechanism to control tight junction regulation in developing vascular beds for tissue engineering scaffolds or understanding vascular growth during developmental processes.</p><p><strong>Conclusion: </strong>Our studies provide novel data for how mechanical phenotype of stromal cells in combination with secreted factor profiles is related to cadherin regulation, localization, and vascularization potential in 3D microtissue models.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"446-463"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069971","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}