{"title":"Generation of Advanced Blood–Brain Barrier Spheroids Using Human-Induced Pluripotent Stem Cell-Derived Brain Capillary Endothelial-Like Cells","authors":"Sanjana Mathew-Schmitt, Sabrina Oerter, Evelin Reitenbach, Sabine Gätzner, Alevtina Höchner, Heinz-Georg Jahnke, Jörg Piontek, Winfried Neuhaus, Andreas Brachner, Marco Metzger, Antje Appelt-Menzel","doi":"10.1002/adbi.202400442","DOIUrl":"10.1002/adbi.202400442","url":null,"abstract":"<p>Extensively studied blood–brain barrier (BBB) in-vitro models are established on 2D cell culture inserts. However, they do not accurately represent 3D in-vivo microenvironments due to lack of direct neurovascular unit cellular contacts. Here, the establishment and characterization of a self-assembled 3D BBB spheroid model using human-induced pluripotent stem cell (hiPSC)-derived brain capillary endothelial-like cells (iBCECs) in combination with primary human astrocytes (ACs) and pericytes (PCs) are reported. This investigation compares 3D spheroids with 2D mono-cultured iBCECs derived from two different hiPSC lines and two differentiation strategies. It is observed that spheroid properties vary depending on the differentiation strategy or type of hiPSC line applied for model generation. However, spheroids demonstrate in-vivo like tight junction ultrastructure and, in comparison to 2D models, higher transcript expression of BBB specific genes. Furthermore, they possess characteristic barrier integrity, barrier functionality, and protein expression. It is inferred that hiPSC-derived BBB spheroids hold a strong potential as a reliable future BBB in-vitro test system.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"9 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adbi.202400442","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2025-01-30DOI: 10.1002/adbi.202400626
Sharda Yadav, Sanjaya KC, Mark A. T. Blaskovich, Cu-tai Lu, Alfred K Lam, Nam-Trung Nguyen
{"title":"RhoA and Rac1 as Mechanotransduction Mediators in Colorectal Cancer","authors":"Sharda Yadav, Sanjaya KC, Mark A. T. Blaskovich, Cu-tai Lu, Alfred K Lam, Nam-Trung Nguyen","doi":"10.1002/adbi.202400626","DOIUrl":"10.1002/adbi.202400626","url":null,"abstract":"<p>Colorectal cancer (CRC) remains a leading cause of cancer-related deaths, creating an urgent need for innovative diagnostic solutions. Mechanobiology, a cutting-edge field that investigates how physical forces influence cell behavior, is now revealing new insights into cancer progression. This research focuses on two crucial players: RhoA and Rac1, small yet powerful proteins that regulate the structure and movement of cancer cells. RhoA controls cell adhesion and migration, while Rac1 drives cell movement and invasion. As CRC tumors grow and reshape the colon's mechanical environment, these pathways become disrupted, accelerating cancer progression. Examining the level of RhoA and Rac1 in CRC clinical samples under mechanical strain reveals their potential as diagnostic markers. Tracking the activity of these proteins can unlock valuable insights into cancer cell dissemination, offering new avenues for understanding and diagnosing CRC. This approach holds promise for earlier detection and better outcomes by offering key insights for more effective diagnostic strategies.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"9 8","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adbi.202400626","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2025-01-22DOI: 10.1002/adbi.202400713
Arturo Bevilacqua, Cristiano Giuliani, Giovanna Di Emidio, Samuel H Myers, Vittorio Unfer, Carla Tatone
{"title":"Murine Models and Human Cell Line Models to Study Altered Dynamics of Ovarian Follicles in Polycystic Ovary Syndrome","authors":"Arturo Bevilacqua, Cristiano Giuliani, Giovanna Di Emidio, Samuel H Myers, Vittorio Unfer, Carla Tatone","doi":"10.1002/adbi.202400713","DOIUrl":"10.1002/adbi.202400713","url":null,"abstract":"<p>Polycystic ovary syndrome is one of the most common endocrine disorders in women of reproductive age, characterized by functional and structural alterations of the female reproductive organs. Due to the unknown underlying molecular mechanisms, in vivo murine models and in vitro human cellular models are developed to study the syndrome. These models are used to analyze various aspects of the pathology by replicating the conditions of the syndrome. Even though the complexity of polycystic ovary syndrome and the challenge of reproducing all its features leave several questions unanswered, studies conducted to date have elucidated some of the alterations in ovarian follicle molecular and cellular mechanisms involved in the syndrome, and do not require the employment of complex and invasive techniques on human patients. This review examines ovarian functions and their alterations in polycystic ovary syndrome, explores preclinical in vivo and in vitro models, and highlights emerging research and medical perspectives. It targets researchers, healthcare professionals, and academics, including endocrinologists, cell biologists, and reproductive medicine specialists, studying the molecular and cellular mechanisms of the syndrome.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"9 7","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adbi.202400713","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2025-01-22DOI: 10.1002/adbi.202400549
Qin Jiang, Xiang Lin, Mimi Zhai, Yi Gong, Yamin Li, Sushun Liu
{"title":"The Role of ROS and Its Sources in Tumorigenesis: Friend or Foe?","authors":"Qin Jiang, Xiang Lin, Mimi Zhai, Yi Gong, Yamin Li, Sushun Liu","doi":"10.1002/adbi.202400549","DOIUrl":"10.1002/adbi.202400549","url":null,"abstract":"<p>Ponicidin has demonstrated effectiveness against HCC by promoting mitochondria apoptosis and generating ROS through the stabilization of the Keap1-PGAM5 complex. However, ROS can exhibit both tumor-promoting and tumor-suppressing activities in cancers, and exhibit different effects depending on its source—mtROS vs non-mtROS. Additionally, since ROS from different sources possesses distinct functions, mitochondria-targeted antioxidants, and non-targeted antioxidants may have entirely different effects on cancer progression. To address this complexity, novel measurement techniques such as MitoSOX, MitoPY1, and siDMA are used to specifically assess mtROS, providing deeper insights into mitochondrial function during treatment. Therefore, distinguishing the sources of ROS and separately detecting and targeting mtROS and non-mtROS can further clarify the anti-tumor mechanisms of ponicidin and provide a foundation for subsequent research.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"9 7","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2025-01-11DOI: 10.1002/adbi.202400408
S. Sergio, B. Spedicato, G. Corallo, A. Inguscio, M. Greco, D. Musarò, D. Vergara, A. F. Muro, G. De Sabbata, L. R. Soria, N. Brunetti Pierri, M. Maffia
{"title":"β-Catenin/c-Myc Axis Modulates Autophagy Response to Different Ammonia Concentrations","authors":"S. Sergio, B. Spedicato, G. Corallo, A. Inguscio, M. Greco, D. Musarò, D. Vergara, A. F. Muro, G. De Sabbata, L. R. Soria, N. Brunetti Pierri, M. Maffia","doi":"10.1002/adbi.202400408","DOIUrl":"10.1002/adbi.202400408","url":null,"abstract":"<p>Ammonia a by-product of nitrogen containing molecules is detoxified by liver into non-toxic urea and glutamine. Impaired ammonia detoxification leads to hyperammonemia. Ammonia has a dual role on autophagy, it acts as inducer at low concentrations and as inhibitor at high concentrations. However, little is known about the mechanisms responsible for this switch. Wnt/β-catenin signalling is emerging for its role in the regulation of ammonia metabolizing enzymes and autophagosome synthesis through c-Myc. Here, using Huh7 cell line, we show a modulation in c-Myc expression under different ammonia concentrations. An increase in c-Myc expression and in its transcriptional regulator β-catenin was detected at low concentrations of ammonia, when autophagy is active, whereas these modifications were lost under high ammonia concentrations. These observations were also recapitulated in the livers of spf-ash mice, a model of constitutive hyperammonaemia due to deficiency in ornithine transcarbamylase enzyme. Moreover, c-Myc-mediated activation of autophagy plays a cytoprotective role in cells under ammonia stress conditions as confirmed through the pharmacological inhibition of c-Myc in Huh7 cells treated with low ammonia concentrations. In conclusion, the unravelled role of c-Myc in modulating ammonia induced autophagy opens new landscapes for the development of novel strategies for the treatment of hyperammonemia.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"9 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adbi.202400408","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2025-01-06DOI: 10.1002/adbi.202400538
Joaquin Montilla-Rojo, Thomas F. Eleveld, Marnix van Soest, Sanne Hillenius, Dennis M. Timmerman, Ad J. M. Gillis, Bernard A. J. Roelen, Christine L. Mummery, Leendert H. J. Looijenga, Daniela C. F. Salvatori
{"title":"Depletion of TP53 in Human Pluripotent Stem Cells Triggers Malignant-Like Behavior","authors":"Joaquin Montilla-Rojo, Thomas F. Eleveld, Marnix van Soest, Sanne Hillenius, Dennis M. Timmerman, Ad J. M. Gillis, Bernard A. J. Roelen, Christine L. Mummery, Leendert H. J. Looijenga, Daniela C. F. Salvatori","doi":"10.1002/adbi.202400538","DOIUrl":"10.1002/adbi.202400538","url":null,"abstract":"<p>Human pluripotent stem cells (hPSCs) tend to acquire genetic aberrations upon culture in vitro. Common aberrations are mutations in the tumor suppressor <i>TP53</i>, suspected to confer a growth-advantage to the mutant cells. However, their full impact in the development of malignant features and safety of hPSCs for downstream applications is yet to be elucidated. Here, <i>TP53</i> is knocked out in hPSCs using CRISPR-Cas9 and compared them with isogenic wild-type hPSCs and human germ cell tumor lines as models of malignancy. While no major changes in proliferation, pluripotency, and transcriptomic profiles are found, mutant lines display aberrations in some of the main chromosomal hotspots for genetic abnormalities in hPSCs. Additionally, enhanced clonogenic and anchorage-free growth, alongside resistance to chemotherapeutic compounds is observed. The results indicate that common <i>TP53</i>-depleting mutations in hPSCs, although potentially overlooked by standard analyses, can impact their behavior and safety in a clinical setting.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"9 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adbi.202400538","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2024-12-31DOI: 10.1002/adbi.202400623
Farbod Ebrahimi, Anjali Kumari, Samaneh Ghadami, Saqer Al Abdullah, Kristen Dellinger
{"title":"The Potential for Extracellular Vesicles in Nanomedicine: A Review of Recent Advancements and Challenges Ahead","authors":"Farbod Ebrahimi, Anjali Kumari, Samaneh Ghadami, Saqer Al Abdullah, Kristen Dellinger","doi":"10.1002/adbi.202400623","DOIUrl":"10.1002/adbi.202400623","url":null,"abstract":"<p>Extracellular vesicles (EVs) have emerged as promising tools in diagnostics and therapy for chronic diseases, including cancer and Alzheimer's. Small EVs, also called exosomes, are lipid-bound particles (≈30–150 nm) that play a role in healthy and pathophysiological interactions, including intercellular communication, by transporting bioactive molecules, including proteins, lipids, and nucleic acids. Their ability to cross biological barriers, such as the blood-brain barrier, makes them ideal candidates for targeted therapeutic interventions. In the context of chronic diseases, exosomes can be engineered to deliver active agents, including small molecules and siRNAs to specific target cells, providing a novel approach to precision medicine. Moreover, exosomes show great promise as repositories for diagnostic biomarkers. Their cargo can reflect the physiological and pathological status of the parent cells, making them valuable indicators of disease progression and response to treatment. This paper presents a comprehensive review of the application of exosomes in four chronic diseases: cancer, cardiovascular disease, neurodegenerative disease, and orthopedic disease, which significantly impact global public health due to their high prevalence and associated morbidity and mortality rates. Furthermore, the potential of exosomes as valuable tools for theranostics and disease management is highlighted. Finally, the challenges associated with exosomes and their demonstrated potential for advancing future nanomedicine applications are discussed.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"9 8","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2024-12-18DOI: 10.1002/adbi.202400483
Andrea Belluati, Adrian Bloch, Kaloian Koynov, Mariana Müller Nieva, Mohadeseh Bagherabadi, Annette Andrieu-Brunsen, Harald Kolmar, Nico Bruns
{"title":"Characterization and Optimization of Vesicle Properties in bioPISA: from Size Distribution to Post-Assembly Loading","authors":"Andrea Belluati, Adrian Bloch, Kaloian Koynov, Mariana Müller Nieva, Mohadeseh Bagherabadi, Annette Andrieu-Brunsen, Harald Kolmar, Nico Bruns","doi":"10.1002/adbi.202400483","DOIUrl":"10.1002/adbi.202400483","url":null,"abstract":"<p>This study investigates the formation and properties of vesicles produced via biocatalytic Polymerization-Induced Self-Assembly (bioPISA) as artificial cells. Methods for achieving size uniformity, including gentle centrifugation and sucrose gradient centrifugation, are explored, and the effects of stirring speed on vesicle morphology is investigated. The internal structure of the vesicles, characterized by a polymer-rich matrix, is analyzed using fluorescence correlation spectroscopy (FCS). Additionally, the feasibility of loading macromolecules into pre-formed vesicles is demonstrated using electroporation, and a fluorescent protein as well as enzymes for a cascade reaction were sucesfully incorporated into the fully assembled polymersomes. These findings provide a foundation for developing enzyme-synthesized polymeric vesicles with controlled morphologies for various applications, e.g., in synthetic biology.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"9 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adbi.202400483","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2024-12-14DOI: 10.1002/adbi.202400358
Qixiang Gui, Neng Ding, Haimei Wu, Jinyue Liu, Yingnan Geng, Jie Zhu, Mingyue Gao, Antong Du, Bingbing Yue, Lie Zhu
{"title":"Development of a pH-Responsive Antimicrobial and Potent Antioxidant Hydrogel for Accelerated Wound Healing: A Game Changer in Drug Delivery","authors":"Qixiang Gui, Neng Ding, Haimei Wu, Jinyue Liu, Yingnan Geng, Jie Zhu, Mingyue Gao, Antong Du, Bingbing Yue, Lie Zhu","doi":"10.1002/adbi.202400358","DOIUrl":"10.1002/adbi.202400358","url":null,"abstract":"<p>Stimuli-responsive hydrogels have the capability to alter their state in response to changes in physiological signals within their application environment, providing distinct benefits in drug delivery applications. Here, the acidic pH typically found in acutely infected wounds can be effectively managed by incorporating a pH-responsive Ag<sup>+</sup> loaded system within the hydrogel, thereby ensuring efficient drug use and preventing potential toxicity from the sudden release of silver ions. The antimicrobial composite hydrogel HAMA/GelMA-CA/Ag<sup>+</sup> provides some tissue adhesion and accelerates wound healing. GelMA-CA is synthesized by modifying gelatin methacryloyl (GelMA) with caffeic acid (CA), while hyaluronic acid methacryloyl (HAMA) is introduced to prepare a double network hydrogel. Silver nitrate is then introduced to make it pH-responsive through the formation of coordination between the polyphenolic structure of caffeic acid and the silver ions. The composite hydrogel exhibited excellent antioxidant properties and strong antimicrobial activity against both Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Furthermore, the composite hydrogel accelerated the promotion of wound healing in a rat model of S. aureus-infected wounds. In conclusion, the HAMA/GelMA-CA/Ag<sup>+</sup> hydrogel is a promising bioactive material that can be used as a wound dressing to promote the healing of acutely infected wounds.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"9 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}