Article
Cell Biology
Yujin Ahn, Ju-Hyun An, Hae-Jun Yang, Dong Gil Lee, Jieun Kim, Hyebin Koh, Young-Ho Park, Bong-Seok Song, Bo-Woong Sim, Hong J. Lee, Jong-Hee Lee, Sun-Uk Kim
Summary: Recent studies have shown that blood vessel organoids (BVOs) can infiltrate human cerebral organoids and form a blood-brain barrier, creating neural-specific blood-vessel networks that can be maintained for over 50 days.
Review
Biochemistry & Molecular Biology
S. Zolotukhin, L. H. Vandenberghe
Summary: In vivo therapeutic gene transfer is a novel class of medicines that relies on the safe and effective delivery of genetic material. The adeno-associated virus (AAV) vector has emerged as a preferred gene delivery vehicle, allowing for therapeutic gene expression in various clinical indications. Recent trends in AAV capsid engineering focus on enhancing targeting specificity, safety, and endurance, a significant challenge that is being addressed through techniques such as directed evolution, sequence analysis, and machine learning.
TRENDS IN MOLECULAR MEDICINE
(2022)
Article
Cell Biology
Rita Silva-Pedrosa, Jonas Campos, Aline Marie Fernandes, Miguel Silva, Carla Calcada, Ana Marote, Olga Martinho, Maria Isabel Veiga, Ligia R. Rodrigues, Antonio Jose Salgado, Pedro Eduardo Ferreira
Summary: Neural injuries in cerebral malaria patients are a major cause of morbidity and mortality. This study proposes an in vitro system using cellular approaches to study human cerebral malaria. By analyzing gene expression profiles in human brain microvascular endothelial cells (HBMEC) activated by Plasmodium falciparum parasites, specific molecular alterations similar to the blood-brain barrier in cerebral malaria were identified. The impact of HBMEC-P. falciparum-activated secretomes on human brain organoids was evaluated to gain a deeper understanding of the physiological mechanisms underlying cerebral malaria.
Article
Cell & Tissue Engineering
Xuerui Yao, Ji Hyun Kang, Kee-Pyo Kim, Hyogeun Shin, Zhe-Long Jin, Hao Guo, Yong-Nan Xu, Ying-Hua Li, Sai Hali, Jeongwoo Kwon, Hyeonwoo La, Chanhyeok Park, Yong-June Kim, Lin Wang, Kwonho Hong, Qilong Cao, Il-Joo Cho, Nam-Hyung Kim, Dong Wook Han
Summary: This study describes a high-speed and large-scale production method for midbrain organoids, called micro midbrain organoids (mu MOs). mu MOs exhibit a highly uniform morphology and gene expression pattern, and mature within a short period of time. They also show consistent responsiveness to neurotoxin, suggesting their potential for high-throughput drug screening applications.
STEM CELLS INTERNATIONAL
(2023)
Article
Cell Biology
Min Soo Kim, Da-Hyun Kim, Hyun Kyoung Kang, Myung Geun Kook, Soon Won Choi, Kyung-Sun Kang
Summary: Novel brain organoid model systems have been developed from adult dermal fibroblast-derived neural stem cells, exhibiting characteristics of the human cerebral cortex for studying neuronal proliferation and maturation. When subjected to hypoxic injury, reoxygenation restored neuronal cell proliferation but not maturation in these neural organoids, suggesting new opportunities for drug screening and personalized modeling of neurodegenerative diseases.
Article
Multidisciplinary Sciences
Bradley R. Groveman, Natalia C. Ferreira, Simote T. Foliaki, Ryan O. Walters, Clayton W. Winkler, Brent Race, Andrew G. Hughson, Gianluigi Zanusso, Cathryn L. Haigh
Summary: The study demonstrates the potential of using human cerebral organoids as a model for screening therapeutic drug candidates for human prion diseases, showing success in identifying an anti-CJD drug through this model.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Santiago Ramirez, Abhisek Mukherjee, Sofia Sepulveda, Andrea Becerra-Calixto, Nicolas Bravo-Vasquez, Camila Gherardelli, Melissa Chavez, Claudio Soto
Summary: The study successfully adapted the controlled cortical impact (CCI) model for inducing traumatic brain injury (TBI) in human cerebral organoids (COs) derived from induced pluripotent stem cells (iPSCs), showing that COs recapitulate primary pathological changes of TBI. This novel approach using human COs in vitro holds great potential for understanding and treating TBI.
Article
Neurosciences
David Goertsen, Nicholas C. Flytzanis, Nick Goeden, Miguel R. Chuapoco, Alexander Cummins, Yijing Chen, Yingying Fan, Qiangge Zhang, Jitendra Sharma, Yangyang Duan, Liping Wang, Guoping Feng, Yu Chen, Nancy Y. Ip, James Pickel, Viviana Gradinaru
Summary: The study developed AAV capsids that achieved robust transgene expression in the brain with decreased liver targeting after non-invasive administration, enabling more targeted systemic gene delivery. This organ-specific targeting extends to marmosets, allowing for non-invasive gene delivery with distinct transgene expression patterns. The ability to cross the blood-brain barrier with neuronal specificity in rodents and non-human primates opens up new avenues for basic research and therapeutic possibilities beyond naturally occurring serotypes.
NATURE NEUROSCIENCE
(2022)
Article
Cell & Tissue Engineering
Ya-Jie Xu, Pei-Pei Liu, Zhong-Ze Yan, Ting-Wei Mi, Ying-Ying Wang, Qian Li, Zhao-Qian Teng, Chang-Mei Liu
Summary: The study revealed that MECP2 deletion led to reduced neuron numbers and simplified dendritic morphology, while treatment with small molecules KW-2449 and VPA, which activate the PI3K-AKT signaling pathway, could alleviate neuronal deficits in RTT models. These findings suggest that KW-2449 and VPA may be promising drugs for the treatment of Rett syndrome.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Neurosciences
Aaron Gordon, Se-Jin Yoon, Stephen S. Tran, Christopher D. Makinson, Jin Young Park, Jimena Andersen, Alfredo M. Valencia, Steve Horvath, Xinshu Xiao, John R. Huguenard, Sergiu P. Pasca, Daniel H. Geschwind
Summary: Research shows that three-dimensional human cortical organoids can reach stages of postnatal brain development after being cultured for 250 to 300 days, paralleling in vivo development. These findings provide important insights and tools for modeling neurodevelopmental diseases.
NATURE NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Mohammadsharif Tabebordbar, Kim A. Lagerborg, Alexandra Stanton, Emily M. King, Simon Ye, Liana Tellez, Allison Krunnfusz, Sahar Tavakoli, Jeffrey J. Widrick, Kathleen A. Messemer, Emily C. Troiano, Behzad Moghadaszadeh, Bryan L. Peacker, Krystynne A. Leacock, Naftali Horwitz, Alan H. Beggs, Amy J. Wagers, Pardis C. Sabeti
Summary: Evolved capsid variants of AAVs show enhanced potency and therapeutic efficacy for delivering genetic modifiers to muscle tissues, surpassing naturally occurring AAV capsids in mouse models of genetic muscle disease. These engineered vectors demonstrate conserved efficacy across different mouse strains, cynomolgus macaques, and human primary myotubes, indicating a promising approach for gene therapy.
Review
Biochemistry & Molecular Biology
Xiao-Yan Tang, Shanshan Wu, Da Wang, Chu Chu, Yuan Hong, Mengdan Tao, Hao Hu, Min Xu, Xing Guo, Yan Liu
Summary: Organoids are 3D miniature structures cultured in vitro that recapitulate the cellular heterogeneity, structure, and functions of human organs. They have potential applications for studying human physiology and development, as well as for biomedical research and preclinical drug testing.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Neurosciences
Brittany Bodnar, Yongang Zhang, Jinbiao Liu, Yuan Lin, Peng Wang, Zhengyu Wei, Sami Saribas, Yuanjun Zhu, Fang Li, Xu Wang, Wenli Yang, Qingsheng Li, Wen-Zhe Ho, Wenhui Hu
Summary: Human cerebral organoids (CO) mimic developing human brains in a 3D cell culture system. Despite some limitations like variability and missing cell types, a novel, scalable system has been introduced for generating microglia-containing CO (MCO) that reflect human brain development with microglia, astrocytes, neurons, and neural stem/progenitor cells. This simplified MCO generation technique involves transitioning from 3D cultures to orbital shaking culture, offering an accessible and affordable system for any general lab.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Medicine, Research & Experimental
Seongmin Jang, Hao K. Shen, Xiaozhe Ding, Timothy F. Miles, Viviana Gradinaru
Summary: This study reports the structure of PHP.eB and its interaction with AAV receptor, revealing that the insertion of amino acid loop in PHP.eB alters the interaction between AAVR and LY6A, thereby changing the tissue targeting of the virus. This suggests that this approach can be used to improve AAV selection.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Biochemical Research Methods
Zheng Ao, Hongwei Cai, Zhuhao Wu, Jonathan Ott, Huiliang Wang, Ken Mackie, Feng Guo
Summary: Researchers developed a controllable acoustofluidic method to improve the standardization of fused organoid models by effectively modeling the development of human mesocortical pathways. They successfully manipulated neuroepithelial bud alignment in acoustically fused human forebrain and midbrain organoids, demonstrating regulation of neuronal projection and progenitor cell division. This approach offers a label-free, contact-free, and highly biocompatible tool for assembling organoids and enhancing disease modeling and tissue engineering.
Article
Immunology
Dirkje de Blauw, Andrea H. L. Bruning, Katja C. Wolthers, Anne-Marie Van Wermeskerken, Maarten H. Biezeveld, Joanne G. Wildenbeest, Dasja Pajkrt
Summary: Supplemental Digital Content is provided in the text.
PEDIATRIC INFECTIOUS DISEASE JOURNAL
(2022)
Article
Cardiac & Cardiovascular Systems
L. Wu, R. W. Emmens, J. van Wezenbeek, W. Stooker, C. P. Allaart, A. B. A. Vonk, A. C. van Rossum, K. C. Wolthers, H. W. M. Niessen, P. A. J. Krijnen
Summary: The presence of viral genomes is not increased in the atria of AF patients, suggesting that viral infection of the atria may not play an important role in the pathogenesis of AF.
NETHERLANDS HEART JOURNAL
(2022)
Letter
Pediatrics
Amrita Biharie, Maya W. Keuning, Katja C. Wolthers, Dasja Pajkrt
WORLD JOURNAL OF PEDIATRICS
(2022)
Review
Virology
Josse A. Depla, Lance A. Mulder, Renata Vieira de Sa, Morgane Wartel, Adithya Sridhar, Melvin M. Evers, Katja C. Wolthers, Dasja Pajkrt
Summary: Brain organoid models, generated from human derived stem cells in three dimensions, have been increasingly used as brain models in virology research, providing valuable insight into the pathogenesis of neurotropic viral infections and testing of antivirals. However, there are limitations in organoid heterogeneity and the absence of microglia and a blood brain barrier.
Article
Multidisciplinary Sciences
Georgios Stroulios, Tyler Brown, Giulia Moreni, Douglas Kondro, Alessandro Dei, Allen Eaves, Sharon Louis, Juan Hou, Wing Chang, Dasja Pajkrt, Katja C. Wolthers, Adithya Sridhar, Salvatore Simmini
Summary: Airway organoids, which mimic the structure and function of in vivo tissue, provide a better model for studying host-pathogen interactions by overcoming the limitations of traditional models. This study introduces a new method to generate airway organoids with an externally exposed apical side, allowing for higher throughput in vitro studies.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Rosalie S. N. Linssen, Adithya Sridhar, Giulia Moreni, Nicole N. van der Wel, Job B. M. van Woensel, Katja C. Wolthers, Reinout A. Bem
Summary: Research using human airway epithelial cell cultures showed that in the context of RSV infection, NETs did not cause or exacerbate epithelial injury or inflammation.
Article
Multidisciplinary Sciences
Jennifer Cable, Mark R. Denison, Margaret Kielian, William T. Jackson, Ralf Bartenschlager, Tero Ahola, Suchetana Mukhopadhyay, Daved H. Fremont, Richard J. Kuhn, Ashleigh Shannon, Meredith N. Frazier, Kwok-Yung Yuen, Carolyn B. Coyne, Katja C. Wolthers, Guo-Li Ming, Camy S. Guenther, Jasmine Moshiri, Sonja M. Best, John W. Schoggins, Kellie Ann Jurado, Gregory D. Ebel, Alexandra Schafer, Lisa F. P. Ng, Marjolein Kikkert, Alessandro Sette, Eva Harris, Peter A. C. Wing, Julie Eggenberger, Siddharth R. Krishnamurthy, Marcus G. Mah, Rita M. Meganck, Donghoon Chung, Sebastian Maurer-Stroh, Raul Andino, Bette Korber, Stanley Perlman, Pei-Yong Shi, Montserrat Barcena, Sophie-Marie Aicher, Michelle N. Vu, Devin J. Kenney, Brett D. Lindenbach, Yukiko Nishida, Laurent Renia, Evan P. Williams
Summary: Positive-strand RNA viruses, such as Zika virus, SARS, and SARS-CoV-2, have caused major outbreaks and epidemics in recent years. The Keystone Symposium Positive-Strand RNA Viruses, held on June 18-22, 2022, brought together researchers in various fields to discuss the latest research in molecular and cell biology, virology, immunology, vaccinology, and antiviral drug development. This report provides concise summaries of the scientific discussions at the symposium.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Clinical Neurology
Stephanie Dooves, Liza M. L. Kok, Dwayne B. Holmes, Nicole Breeuwsma, Marjolein Breur, Marianna Bugiani, Nicole Wolf, Vivi M. Heine
Summary: Using iPSC-derived cultures, researchers found reduced ARX expression, increased neuronal network activity, and altered development of interneurons-particularly parvalbumin lineage-in patients with 4H leukodystrophy, a rare white matter disorder. 4H is a rare genetic disorder characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. The discovery of the role of RNA polymerase III mutations in 4H has expanded the understanding of the disease beyond its classic phenotype. This study's importance rating is 8 out of 10.
Article
Cell Biology
Kevin L. Batenburg, Nael N. Kasri, Vivi M. Heine, Wiep Scheper
Summary: Progressive tau protein aggregation in neurons is associated with neurodegeneration in tauopathies. This study investigates the role of astrocytes in the disease process and demonstrates that intraneuronal tau aggregation induces oxidative stress and activation of the integrated stress response specifically in astrocytes. Tau-directed antisense therapy reduces tau levels and aggregation and prevents cell non-autonomous responses in astrocytes, providing evidence of its efficacy in targeting disease pathways in a human tau pathology model.
JOURNAL OF MOLECULAR CELL BIOLOGY
(2023)
Article
Biochemical Research Methods
Kevin L. Batenburg, Claudia Sestito, Paulien Cornelissen-Steijger, Jan R. T. van Weering, Leo S. Price, Vivi M. Heine, Wiep Scheper
Summary: In this study, a novel 3D human neuron/astrocyte co-culture model was established to investigate cell type-specific manipulations associated with neurodegenerative disorders. The results showed that this model accurately mirrors the three-dimensional architecture of the human brain and successfully introduced intraneuronal tau aggregation, providing a potential platform to study neuron-astrocyte interaction.
BIOLOGICAL PROCEDURES ONLINE
(2023)
Article
Cell Biology
Chantal Scheepbouwer, Ernesto Aparicio-Puerta, Cristina Gomez-Martin, Heleen Verschueren, Monique van Eijndhoven, Laurine E. Wedekind, Stavros Giannoukakos, Nathalie Hijmering, Lisa Gasparotto, Hilde T. van der Galien, Roos S. van Rijn, Eleonora Aronica, Robby Kibbelaar, Vivi M. Heine, Pieter Wesseling, David P. Noske, W. Peter Vandertop, Daphne de Jong, D. Michiel Pegtel, Michael Hackenberg, Tom Wurdinger, Alan Gerber, Danijela Koppers-Lalic
Summary: Transfer RNAs (tRNAs) play a vital role in mRNA translation, and changes in tRNA composition can directly impact cancer development and progression. To accurately assess tRNA expression and fragmentation levels, the ALL-tRNAseq technique was developed, which combines MarathonRT, RNA demethylation, and randomized adapter ligation prior to reverse transcription. This approach greatly improves the classification of oncogenic signatures in glioblastoma and diffuse large B-cell lymphoma tissues, particularly in samples with higher levels of RNA fragmentation.
GENES & DEVELOPMENT
(2023)
Article
Cell Biology
Fatma Masmoudi, Nanci Santos-Ferreira, Dasja Pajkrt, Katja C. C. Wolthers, Jeroen DeGroot, Maria L. H. Vlaming, Joana Rocha-Pereira, Ludovico Buti
Summary: Enteroviruses cause various infections, but specific antiviral treatments are lacking. Organoids provide a valuable model for studying antiviral treatments, and comparing them to conventional cell lines can enhance understanding. Our study shows that human small intestinal organoids are more sensitive to enterovirus infection and drug treatment, highlighting the importance of using organoid models in antiviral studies.
Article
Virology
Giulia Moreni, Hetty van Eijk, Gerrit Koen, Nina Johannesson, Carlemi Calitz, Kimberley Benschop, Jeroen Cremer, Dasja Pajkrt, Adithya Sridhar, Katja Wolthers
Summary: This study investigated the tissue and cellular tropism of non-polio enteroviruses (EV) belonging to species C, which are highly prevalent in Africa, mainly among children. The results showed that these viruses can replicate in both the human airway and intestinal organotypic cultures, with ciliated airway cells and enterocytes being the target of infection.