{"title":"Recent progress in 2D, 3D, and on-a-chip models of the placenta.","authors":"Alexandra M Harrison, Christina M Bailey-Hytholt","doi":"10.1159/000547560","DOIUrl":"https://doi.org/10.1159/000547560","url":null,"abstract":"<p><strong>Background: </strong>The placenta is a temporary organ that develops throughout pregnancy, connecting a developing fetus to the maternal uterine wall. The placenta's structure is species specific and complex, resulting in recent advancements with in vitro models to help study this dynamic organ. The main cell type composing the placenta, trophoblast cells, serve several roles and have been incorporated within biomaterials and devices to recapitulate the placental microenvironment.</p><p><strong>Summary: </strong>This review highlights in vitro 2D, 3D, and on-a-chip models of two placental interfaces: the interface between the endometrium and extravillous trophoblast cells and the interface between the chorionic villi and intervillous space. First, an overview of placental cell types and in vitro model types used in the discussed studies is provided. Next, models of invasive trophoblasts cells at the endometrium where the placenta is anchored and the spiral arteries are remodeled are discussed. Next, the review highlights models of the chorionic villi and intervillous space, an interface where cytotrophoblast cells fuse into syncytiotrophoblasts. Finally, we discuss key takeaways and future directions in creating representative placental models.</p><p><strong>Key messages: </strong>The combination of biomaterial and engineering approaches has led to the development of physiologically relevant models, allowing placental trophoblast functions to be investigated with more clarity. Each cell type (e.g. trophoblast cell line vs. stem cells vs. primary placental cells) and biomaterial system (e.g. organoid vs. on-a-chip) that is selected for a given model has a unique combination of advantages and limitations, which are detailed within this review. Overall, the placental models discussed enable trophoblast cell behavior to be studied in vitro with the inclusion of extracellular matrix materials, growth factors, and other environmental cues. While one model alone does not fully recapitulate every function of the placenta, individual models are tailored to inform on specific placental trophoblast behaviors.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-50"},"PeriodicalIF":1.9,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728299","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}
Meghana Madabhushi, Rachel Erin Murphy, Md Akkas Ali, Muthuvel Paneerselvam, Mallikarjun Hanamantagouda Patil, Daniel J Tyrrell, Juhi Samal
{"title":"Mitochondrial Glycosylation in Neuroinflammation Models.","authors":"Meghana Madabhushi, Rachel Erin Murphy, Md Akkas Ali, Muthuvel Paneerselvam, Mallikarjun Hanamantagouda Patil, Daniel J Tyrrell, Juhi Samal","doi":"10.1159/000547463","DOIUrl":"https://doi.org/10.1159/000547463","url":null,"abstract":"<p><strong>Introduction: </strong>Mitochondria are cellular energy factories, but their function declines with age in many tissues as well as disease pathophysiology. Mitochondrial proteins have sugar modifications called glycans, which regulate their function and localization. There is a knowledge gap on the impact of mitochondrial protein glycosylation on mitochondrial function and mediating neuroinflammation. We hypothesize that stimuli-specific neuroinflammatory treatments in microglia induce pathological changes in mitochondrial protein glycosylation and compromise mitochondrial function.</p><p><strong>Methods: </strong>The aim of this study was to establish a detailed microglial mitochondrial glycoprofile in different models of inflammation using lectins to identify the glycan-based markers of mitochondrial dysfunction. We use three different pathways of microglial activation: lipopolysaccharide (LPS), cytokines, and oxygen-glucose deprivation (OGD), revealing differences in mitochondrial glycosylation in different models of inflamed microglia. Mitochondrial lectin blots and lectin flow analysis were used to quantify the glycosylation changes due to different neuroinflammatory conditions. Seahorse Mito Stress assay was performed to assess mitochondrial function in each of these conditions.</p><p><strong>Results: </strong>Lectin immunoblots of mitochondrial proteins and lectin flow studies with intact mitochondria were performed in three different neuroinflammation models using BV-2 microglial cells, revealing considerable stimuli-specific, differential mitochondrial glycosylation between these models and healthy controls. It was found that several glycans associated with mitochondria were differentially regulated during microglial activation. The observed changes in glycosylation trends were more drastic in OGD treatment as compared to other treatments, especially for complex and sialylated glycans.</p><p><strong>Conclusion: </strong>This study represents the first functional investigation of mitochondrial glycosylation in microglial inflammation models towards identifying glycosylation-based therapeutic targets.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-25"},"PeriodicalIF":2.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706335","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}
Ana I Gonçalves, Lucrezia Righelli, Rui L Reis, Alicia J El Haj, Manuela E Gomes
{"title":"Understanding degeneration and healing pathways for tissue engineered treatment strategies in tendinopathy.","authors":"Ana I Gonçalves, Lucrezia Righelli, Rui L Reis, Alicia J El Haj, Manuela E Gomes","doi":"10.1159/000547258","DOIUrl":"https://doi.org/10.1159/000547258","url":null,"abstract":"<p><p>The multidisciplinary nature of the tendon tissue engineering field brings challenges to move from our basic understanding of tendon biology towards engineering strategies for tendon disorders. Such pathologies present a high risk of inflammation for young patients and limited tissue regeneration capability in aging patients, leading to painful symptoms and impaired quality of life. Among the complications observed in tendinopathy are degenerative changes in the extracellular matrix and aberrant tissue remodeling, accounting for a huge burden in musculoskeletal disorders worldwide. This underscores the need for early therapeutic interventions to address tissue degeneration effectively. Moreover, the development of novel therapies lacks insufficient tendinopathy models to search drug efficacy or to model healthy and pathological tissue growth events in physiologically relevant microenvironments. This review focuses on current treatments for tendinopathy, the biological signals involved in tendon healing, and overlook tissue engineering developments in the field.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-29"},"PeriodicalIF":2.9,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574911","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}
Agner Henrique Dorigo Hochuli, Ana Helena Selenko, Mateus de Oliveira Lisboa, Alexandra Cristina Senegaglia, Maria Luiza de Castro, Joselito Getz, Letícia Fracaro, Paulo Roberto Slud Brofman
{"title":"Mesenchymal Stromal Cells from Dental Tissues Demonstrate Neuronal Potential Pre- and Post-Induction.","authors":"Agner Henrique Dorigo Hochuli, Ana Helena Selenko, Mateus de Oliveira Lisboa, Alexandra Cristina Senegaglia, Maria Luiza de Castro, Joselito Getz, Letícia Fracaro, Paulo Roberto Slud Brofman","doi":"10.1159/000547257","DOIUrl":"https://doi.org/10.1159/000547257","url":null,"abstract":"<p><strong>Introduction: </strong>Mesenchymal stromal cells (MSCs) play a crucial role in tissue repair and exhibit anti-inflammatory properties, making them promising for regenerative medicine. Dental tissue-derived MSCs, such as stromal cells from human exfoliated deciduous teeth (SHEDs) and dental pulp stromal cells (DPSCs), express neural markers and hold the potential for treating neurodegenerative diseases. Nonetheless, their relative ability to differentiate into neurons is still unclear. Given their shared embryonic origin, we hypothesised that SHEDs and DPSCs possess similar potential for neuronal differentiation along with intrinsic expression of neuronal markers. The objective of this study was to compare their differentiation abilities under standardised conditions and evaluate neuronal markers pro- and post-neuronal induction.</p><p><strong>Objective: </strong>To compare the neuronal differentiation potential of SHEDs and DPSCs.</p><p><strong>Methodology: </strong>SHEDs (n=3) and DPSCs (n=3) were collected with ethical approval, cultured, and characterised according to established MSC criteria. Clonogenicity, proliferation, senescence, and trilineage differentiation were assessed. Neuronal differentiation was induced for 21 days and evaluated using flow cytometry (SRY-Box Transcription Factor 1 (SOX1), SRY-Box Transcription Factor 2 (SOX2), Glial fibrillary acidic protein (GFAP), doublecortin, nestin, CD56, CD146), immunofluorescence for βIII-tubulin, and reverse transcription polymerase chain reaction (RT-PCR) for tubulin 3 (TUB3) and microtubule-associated protein 2 (MAP2).</p><p><strong>Results: </strong>Both SHEDs and DPSCs exhibited MSC characteristics. SHEDs showed higher clonogenicity. Early neuronal markers (e.g., SOX1, Nestin, GFAP, βIII-tubulin) were detected pre- and post-induction in both cell types without significant intergroup differences. No significant expression of TUB3 and MAP2 was observed.</p><p><strong>Conclusion: </strong>SHEDs and DPSCs show comparable neuronal marker expression profiles, suggesting similar early neuronal differentiation potential. These findings support using undifferentiated SHEDs and DPSCs in neuro-regenerative strategies, offering cost-effective and safer alternatives to pre-differentiated cells.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-24"},"PeriodicalIF":2.9,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574910","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":"Boundary Formation of the Human Caudal Foregut during the Early Fetal Period: Three-Dimensional Analysis Using T1-Weighted and Diffusion Tensor Images.","authors":"Toru Kanahashi, Hirohiko Imai, Hiroki Otani, Shigehito Yamada, Jörg Männer, Tetsuya Takakuwa","doi":"10.1159/000546997","DOIUrl":"10.1159/000546997","url":null,"abstract":"<p><strong>Introduction: </strong>While caudal foregut development in human fetuses has been outlined in previous research, the formation of its border region remains unclear. This study aimed to visualize the precise timeline of caudal foregut boundary formation.</p><p><strong>Methods: </strong>Three-dimensional images of the foregut from T1-weighted scans of 24 fetuses (crown-rump length [CRL]: 34-103 mm) were analyzed to measure the wall thickness and lumen diameter at nine specific sites. The internal structure in the border region was verified using histological sections and diffusion tensor imaging (DTI) tractography.</p><p><strong>Results: </strong>The lower esophageal and pyloric canal walls were thicker in samples with a CRL ≥50 mm. The esophageal wall at the esophageal hiatus, where the lower esophageal sphincter is located, was particularly thick in samples with a CRL ≥88 mm. Increased wall thickness at the esophageal hiatus and pyloric canal resulted in a narrower lumen. The pyloric canal lumen narrowed from its distal to proximal sections. The lumen diameter-to-wall thickness ratio at the esophageal hiatus and proximal pyloric was negatively correlated with CRL. The thickened esophageal wall at the esophageal hiatus had a thick submucosa, and all layers in the pyloric canal thickened with growth. DTI tractography revealed that the lower esophageal wall mainly comprised longitudinal fibers, whereas the pyloric canal wall consisted solely of circular fibers, with fractional anisotropy increasing with growth.</p><p><strong>Conclusion: </strong>This study provides a comprehensive timeline of normal caudal foregut boundary formation during the early human fetal period, thereby improving the understanding of congenital foregut obstruction pathogenesis.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-17"},"PeriodicalIF":2.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12283065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367967","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}
{"title":"Development of Soft Palatal Musculature Characterized by the Uvula Muscle of Miniature Pig.","authors":"Min Li, Junwen Huang, Xiaoyu Lin, Kaizhao Guo, Xuechun Li, Songlin Wang, Xiaoshan Wu","doi":"10.1159/000546790","DOIUrl":"10.1159/000546790","url":null,"abstract":"<p><strong>Introduction: </strong>Surgical reconstruction is recommended for cleft palate patients. However, improper muscle reconstruction can cause scarring and velopharyngeal insufficiency. Understanding the developmental patterns of soft palatal musculature is crucial for improving treatments. Although mice are commonly used to investigate soft palate development, the uvula deficiency in mice limits their applicability. This study aimed to compare the developmental characteristics of soft palate muscles in miniature pigs and mice at various stages to better understand the patterns in large mammals.</p><p><strong>Methods: </strong>Specimens of soft palate were collected from human embryos, miniature pigs, and mice at different stages. Furthermore, comprehensive gross observations, haematoxylin and eosin staining, and immunohistochemical analyses for myosin heavy chain and hypermethylated cancer 1 (Hic1) were conducted on multiple dissected sections.</p><p><strong>Results: </strong>Mature soft palatal musculature exhibited anatomical and histological similarities across the three species. Notably, miniature pigs exhibited the uvula structure and uvula muscle (MU) development comparable to humans. Embryonic day 40 (E40, equivalent to human embryonic week 11, E11w) represented the early developmental stage of the MU, characterized by scattered muscle cells not yet coalescing into multinucleated fibres. By E45 (aligned with human E12w), the muscle bundles reached maturity, exhibiting two oriented fibre bundles flanking the midline. Levator veli palatini muscle and palatopharyngeus of miniature pigs exhibited a distinct course pattern due to the presence of the MU. Hic1+ perimysial cells were observed at the extending edge of the developing palatopharyngeus of miniature pigs, indicating a potential guiding role in the migration of myogenic cells.</p><p><strong>Conclusion: </strong>Characterized by the MU, the spatiotemporal dynamic process of soft palatal musculature of miniature pigs was revealed. Miniature pigs exhibit a similar structure of the MU to that of humans and therefore serve as a promising model for researching soft palatal musculature development of large mammals in the future.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-17"},"PeriodicalIF":2.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233313","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}
Cancan Pan, Xuyan Gong, Xuekui Wang, Huiyuan Wu, Yao Sun
{"title":"Cytosolic Carboxypeptidase 1 Loss in Bone Marrow Mesenchymal Stem Cells Inhibited Osteogenic Differentiation by Enhancing Microtubule Glutamylation.","authors":"Cancan Pan, Xuyan Gong, Xuekui Wang, Huiyuan Wu, Yao Sun","doi":"10.1159/000546259","DOIUrl":"10.1159/000546259","url":null,"abstract":"<p><strong>Introduction: </strong>Cytosolic carboxypeptidase 1 (CCP1) is a deglutamylase that antagonizes polyglutamylation. Mutations in human CCP1 gene cause a severe disease known as childhood-onset neurodegeneration with cerebellar atrophy (CONDCA), which is characterized by marked growth retardation. However, the role and mechanisms of CCP1 in skeletal development remain unclear.</p><p><strong>Methods: </strong>In this study, we used CCP1 knockout (CCP1-KO) mice to assess bone mass changes by micro-CT, HE, alkaline phosphatase (ALP) staining, tartrate-resistant acid phosphatase staining and immunofluorescence staining. Changes in osteogenic differentiation, proliferation, and migration capacity of bone marrow mesenchymal stem cells (BMSCs) were assessed by ALP, alizarin red (ARS) staining, quantitative real-time PCR, EdU staining, and cell scratching assay. Then, tubulin glutamylation and primary cilia of BMSCs after deletion of CCP1 was analyzed by Western blot and immunofluorescence staining. Finally, CB839, an inhibitor of glutamine metabolism, was used to detect changes in the osteogenic differentiation ability and primary cilia of BMSCs after reducing the elevated glutamylation level.</p><p><strong>Results: </strong>CCP1-KO mice exhibited phenotypes relevant to humans, including reduced body size, decreased bone mass, and reduced bone density during growth and development. CCP1 deficiency impairs the proliferation, migration, and osteogenic differentiation of BMSCs. Meanwhile, the number of pre-osteoblasts derived from BMSCs is decreased, leading to impaired osteogenesis. At the cellular level, CCP1 loss results in aberrant tubulin glutamylation, increased microtubule glutamylation, and shortened primary cilia in BMSCs. Finally, reduction of abnormally elevated tubulin glutamylation was efficacious for promoting osteogenic differentiation of BMSCs and restoring primary cilia length of BMSCs.</p><p><strong>Conclusion: </strong>We propose that CCP1 plays a critical role in regulating BMSCs differentiation and promotes osteogenesis by modulating the post-translational modifications of tubulin, with a view to provide new targets for the prevention and treatment of hard tissue diseases.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-16"},"PeriodicalIF":2.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987015","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}
Xinrong Lu, Yongliang Tong, Mengting Wu, Shaoxian Lyu, Jiale Fan, Junyu Zheng, Lin Zou, Danfeng Shen, Lin Rao, Linlin Hou, Cuiying Chen, Xunjia Cheng, Guiqin Sun, Zhiyong Shao, Li Chen
{"title":"Downregulation of Endo-Beta-N-Acetylglucosaminidase in Caenorhabditis elegans Improves Stress Adaptivity.","authors":"Xinrong Lu, Yongliang Tong, Mengting Wu, Shaoxian Lyu, Jiale Fan, Junyu Zheng, Lin Zou, Danfeng Shen, Lin Rao, Linlin Hou, Cuiying Chen, Xunjia Cheng, Guiqin Sun, Zhiyong Shao, Li Chen","doi":"10.1159/000546244","DOIUrl":"10.1159/000546244","url":null,"abstract":"<p><strong>Introduction: </strong>Endo-beta-N-acetylglucosaminidase (ENGASE) is one of the key enzymes involved in the structural and functional regulations of glycoproteins. Although its enzymatic activities and applications have been well studied in vitro, its biological function in vivo yet remains to be illustrated. In this study, the biological function of ENGASE in Caenorhabditis elegans was explored in detail.</p><p><strong>Methods: </strong>An Engase gene knockout in C. elegans (CeEng-1 or CeEngase) was constructed and subjected to a panel of phenotypical and glycomics analysis. In addition, in vitro and in vivo ENGASE inhibition assays were performed.</p><p><strong>Results: </strong>Engase knockout worm's adaptivity to environmental stresses (heat and osmotic) was significantly improved, and its longevity was also increased mildly. A clustered change in basement membrane proteins (e.g., LAM-1, LAM-2, and EPI-1) was illustrated by N-glycopeptide analysis, suggesting that ENGASE is involved in a basement membrane-based stress regulation. Then, the heat stress phenotype was further supported by in vivo CeEngase knockdown assay and in vitro and in vivo small compound inhibitory assay of CeENGASE, indicating that ENGASE is a potential drug target for stress management.</p><p><strong>Conclusion: </strong>Engase is actively involved in a basement membrane-mediated stress adaptation and could serve as a potential target for healthcare products.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-15"},"PeriodicalIF":2.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967018","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}
Md Tanvir Morshed, Anne Bernhardt, Maria Wartenberg, Heinrich Sauer
{"title":"Endocytotic Albumin Uptake Pathways in Human Adipose Stem Cells and Connection to Intracellular Calcium Oscillations and the Neonatal Fc receptor.","authors":"Md Tanvir Morshed, Anne Bernhardt, Maria Wartenberg, Heinrich Sauer","doi":"10.1159/000545773","DOIUrl":"10.1159/000545773","url":null,"abstract":"<p><strong>Introduction: </strong>Intracellular Ca2+ oscillations of unknown function occur in human adipose tissue stem cells (ASCs). In the present study, we investigated whether Ca2+ oscillations in ASCs from subcutaneous fat tissue derived from female patients were driving albumin endocytosis by involving the neonatal Fc receptor (FcRn), which is mediating the recycling of albumin and IgG.</p><p><strong>Methods: </strong>Intracellular Ca2+ oscillations were monitored by Fluo-4 microfluorometry. Uptake of fluorescence-labeled albumin was assessed by confocal laser scanning microscopy in the presence of endocytotic pathway inhibitors. FcRn was inactivated either by use of the antagonizing antibody nipocalimab or siRNA technology.</p><p><strong>Results: </strong>Endocytosis of albumin occurred by macropinocytosis (inhibition by cytochalasin D, wortmannin, and ethylisopropylamiloride [EIPA]), caveolae-dependent (inhibition by genistein and nystatin) and clathrin-mediated (inhibition by Dyngo-4a) pathways. In serum-free medium, Ca2+ oscillations were absent, but were induced by the addition of either fetal bovine serum, albumin, IgG or a stimulating antibody against FcRn. Consequently, FcRn expression was demonstrated in ASCs by Western blot analysis and immunohistochemistry, and colocalized with endocytosed albumin. Ca2+ oscillations were inhibited by the Ca2+ chelating agent BAPTA, the store-operated Ca2+ entry inhibitor SKF96365, the Ca2+-sensing receptor (CaSR) inhibitor NPS-2143, the macropinocytosis inhibitors cytochalasin D, wortmannin, and EIPA, the caveolae-dependent endocytosis inhibitors genistein and nystatin, and the clathrin-mediated endocytosis inhibitor Dyngo-4a. Uptake of fluorescence-labeled albumin was inhibited by agents interfering with Ca2+ oscillations and endocytosis blockers. Notably, not only intracellular albumin and IgG accumulation, but also Ca2+ oscillations were inhibited by the FcRn-blocking antibody nipocalimab, which interferes with the IgG binding site of FcRn. Moreover, siRNA-mediated downregulation of FcRn protein expression significantly reduced intracellular albumin content, the number of cells displaying Ca2+ oscillations, and the duration and amplitude of Ca2+ signals.</p><p><strong>Conclusion: </strong>Our data suggest that Ca2+ oscillations in human ASCs regulate albumin uptake and presumably IgG recycling via FcRn.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-20"},"PeriodicalIF":2.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981878","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}
{"title":"Superior Mesenteric Artery during Intestinal Loop Formation and Its Positional Changes from the Extracoelom to the Abdominal Cavity.","authors":"Tetsuya Takakuwa, Maki Kakeya, Nanase Ishida, Toru Kanahashi, Sena Fujii, Jörg Männer, Shigehito Yamada","doi":"10.1159/000545751","DOIUrl":"10.1159/000545751","url":null,"abstract":"<p><strong>Introduction: </strong>Features of the superior mesenteric artery (SMA) and its intestinal branches during the embryonic and early fetal periods have not been fully described. We aimed to comprehensively elucidate the characteristics of intestinal branch artery formation in the SMA.</p><p><strong>Methods: </strong>Serial tissue sections of seven early fetal specimens belonging to the Blechschmidt collection were digitalized and used for segmentation and reconstruction of the intestinal loop, SMA trunk, intestinal branch arteries, and mesentery for further analysis.</p><p><strong>Results: </strong>The intestinal branch arteries fed the intestinal tract from the oral side to the anal side, according to the order of their origin from the root to the periphery of the SMA trunk. SMA and intestinal branches were not as strongly conserved in their morphology as indicated in previous research but varied between specimens. Most intestinal branch arteries exhibited frequent branching with small intervals at the periphery, whereas the proximal branch exhibited few branches. Only a few peripheral branches made contact with the neighboring intestinal branch arteries. The fetal intestinal branch artery architecture differed greatly from that of adults. There were considerable inter- and intra-specimen variations in the intestinal tract length per feeding intestinal branch artery. The SMA branching arteries did not always supply each tertiary loop individually, and not every loop is connected to one branching artery.</p><p><strong>Conclusion: </strong>This study elucidates the characteristics of forming the SMA intestinal branch arteries. Specifically, the findings suggest that the SMA is similar to other arteries in that its branches show a level of variability in feeding tissues.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-12"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810468","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}