{"title":"The Efficacy of Acupuncture Therapy in the Management of Dyspnea and Other Symptoms Associated with Heart Failure: A Consolidated Review of Trial Data.","authors":"Vishnu Ganglani, Yong-Jian Geng","doi":"10.1159/000539593","DOIUrl":"10.1159/000539593","url":null,"abstract":"<p><strong>Introduction: </strong>Acupuncture has been used for pain management for thousands of years. However, it is largely unclear whether this therapeutic approach can effectively reduce heart failure-associated symptoms, including dyspnea. The hypothesis posited in this study was that acupuncture does indeed aid in the management of such symptoms and was motivated by the following statistics that establish a requisite need for efficient management of dyspnea to improve patient outcomes with heart failure. In 2020, an estimated 6.2 million adults in the USA had a heart failure diagnosis; in 2018, 379,800 death certificates reported heart failure; and the national cost of heart failure in 2012 was approximately USD 30.7 billion.</p><p><strong>Methods: </strong>The methodology employed to conduct this study involved review of trial data extracted from review of papers pertaining to acupuncture, symptoms of heart failure, and dyspnea, from academic and clinical data repositories subject to various inclusion and exclusion criteria. Of the initial set of 293 studies identified, the resulting inclusion set comprised 30 studies. The analysis conducted revealed that the highest frequency of combined acupuncture points prescribed for the foregoing search criteria were as follows: BL13, BL23, LU9, LU5, Dingchuan, LI4, PC6, and HT7.</p><p><strong>Results: </strong>A meta-analysis of combined pooled p values for the studies revealed that acupuncture does aid in the management of symptoms of dyspnea and heart failure, subject to various limitations including but not limited to heterogeneity inherent between the studies in the inclusion set that were analyzed. Such limitations underscore the need to restrict generalizations from the conclusions of this study.</p><p><strong>Conclusion: </strong>The impact and novelty of this research study is its attempt to target the apparent paucity of literature that focuses on the management of dyspnea specifically in the context of heart failure with acupuncture and to bridge the gap of the application of acupuncture research on dyspnea to the cardiovascular context of heart failure. Notwithstanding the meta-analysis undertaken under this review study, further statistical analysis and a pilot study are warranted to consolidate or nullify the results of the research.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-24"},"PeriodicalIF":2.9,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199378","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}
Rami Al Meklef, Johannes Kacza, Thomas Kremer, Susanne Rein
{"title":"Periarticular Proprioception: Analyzing the Three-Dimensional Structure of Corpuscular Mechanosensors in the Dorsal Part of the Scapholunate Ligament.","authors":"Rami Al Meklef, Johannes Kacza, Thomas Kremer, Susanne Rein","doi":"10.1159/000538169","DOIUrl":"10.1159/000538169","url":null,"abstract":"<p><strong>Introduction: </strong>Sensory nerve endings transmit mechanical stimuli into afferent neural signals and form the basis of proprioception, giving rise to the self-perception of dynamic stability of joints. We aimed to analyze the three-dimensional structure of periarticular corpuscular sensory nerve endings in a carpal ligament to enhance our understanding of their microstructure.</p><p><strong>Methods: </strong>Two dorsal parts of the scapholunate ligament were excised from two human cadaveric wrist specimens. Consecutive cryosections were stained with immunofluorescence markers protein S100B, neurotrophin receptor p75, protein gene product 9.5 (PGP 9.5), and 4',6-diamidino-2-phenylindole. Three-dimensional images of sensory nerve endings were obtained using confocal laser scanning microscopy, and subsequent analysis was performed using Imaris software.</p><p><strong>Results: </strong>Ruffini endings were characterized by a PGP 9.5-positive central axon, with a median diameter of 4.63 μm and a median of 25 cells. The p75-positive capsule had a range in thickness of 0.94 μm and 15.5 μm, consisting of single to three layers of lamellar cells. Ruffini endings were significantly smaller in volume than Pacini corpuscles or Golgi-like endings. The latter contained a median of three intracorpuscular structures. Ruffini endings and Golgi-like endings presented a similar structural composition of their capsule and subscapular space. The central axon of Pacini corpuscles was surrounded by S100-positive cells forming the inner core which was significantly smaller than the outer core, which was immunoreactive for p75 and PGP 9.5.</p><p><strong>Conclusion: </strong>This study reports new data regarding the intricate outer and intracorpuscular three-dimensional morphology of periarticular sensory nerve endings, including the volume, number of cells, and structural composition. These results may form a basis to differ between normal and pathological morphological changes in periarticular sensory nerve endings in future studies.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847399","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}
Michael Fook-Ho Lee, Daniel Steffens, Johnson H Y Chung, Steven Posniak, Kai Cheng, Jonathan Clark, Gordon Wallace, Payal Mukherjee
{"title":"Co-culture of chondrocytes and stem cells: a review of head and neck cell lines for cartilage regeneration.","authors":"Michael Fook-Ho Lee, Daniel Steffens, Johnson H Y Chung, Steven Posniak, Kai Cheng, Jonathan Clark, Gordon Wallace, Payal Mukherjee","doi":"10.1159/000538461","DOIUrl":"https://doi.org/10.1159/000538461","url":null,"abstract":"<p><strong>Introduction: </strong>Bioprinting, using \"bio-inks\" consisting of living cells, supporting structures and biological motifs to create customized constructs, is an emerging technique that aims to overcome the challenges of cartilaginous reconstruction of head and neck structures. Several living cell lines and culturing methods have been explored as bio-inks with varying efficacy. Co-culture of primary chondrocytes and stem cells (SCs) is one technique, well established for degenerative joint disease treatment, with potential for use in expanding chondrocyte populations for bio-inks. This study aims to evaluate the techniques for co-culture of primary chondrocytes and SCs for head and neck cartilage regeneration.</p><p><strong>Methods: </strong>A literature review was performed through OVID/Web of Science/MEDLINE/BIOSIS Previews/Embase. Studies reporting on chondrocytes and SCs in conjunction with co-culture or cartilage regeneration were included. Studies not reporting on findings from chondrocytes/SCs of the head and neck were excluded. Extracted data included cell sources, co-culture ratios and histological, biochemical and clinical outcomes.</p><p><strong>Results: </strong>15 studies met inclusion criteria. Auricular cartilage was the most common chondrocyte source (n=10), then nasal septum (n=5), articular (n=1) and tracheal cartilage (n=1). Bone marrow was the most common SC source (n=9) then adipose tissue (n=7). Techniques varied, with co-culture ratios ranging from 1:1 to 1:10. All studies reported co-culture to be superior to SC mono-culture by all outcomes. Most studies reported superiority or equivalence of co-culture to chondrocyte mono-culture by all outcomes. When comparing clinical outcomes, co-culture constructs were equivalent to chondrocyte mono-culture in diameter, and equivalent or inferior in wet weight and height.</p><p><strong>Conclusion: </strong>Co-culture of primary chondrocytes and SCs is a promising technique for expanding chondrocyte populations, with at least equivalence to chondrocyte mono-culture and superior to SC mono-culture when seeded at the same chondrocyte densities. However, there remains a lack of consensus regarding the optimal cell sources and co-culture ratios.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140183897","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}