Review
Chemistry, Physical
Bauer L. LeSavage, Riley A. Suhar, Nicolas Broguiere, Matthias P. Lutolf, Sarah C. Heilshorn
Summary: The translation discusses how organotypic models of patient-specific tumors are changing our understanding of cancer heterogeneity and personalized medicine. These models can preserve genetic, proteomic, morphological, and pharmacotypic features of the parent tumor in vitro, and offer genomic and environmental manipulation. However, current cancer organoid culture techniques are uncontrolled and irreproducible, hindering the acceleration of insights into patient care.
Article
Engineering, Biomedical
Han Kyung Kim, Hyeryeon Kim, Myoung Kyu Lee, Woo Hee Choi, Yejin Jang, Jin Soo Shin, Jun-Yeol Park, Dong Hyuck Bae, Seong-In Hyun, Kang Hyun Kim, Hyun Wook Han, Byungho Lim, Gildon Choi, Meehyein Kim, Young Chang Lim, Jongman Yoo
Summary: This study successfully established tonsil epithelial cell-derived organoids and demonstrated their feasibility as an ex vivo model for SARS-CoV-2 infection. The organoids recapitulated key characteristics of tonsil epithelium and expressed molecules essential for viral entry. Additionally, gene expression changes were observed in the organoids after SARS-CoV-2 infection, and the antiviral drug remdesivir showed efficacy in suppressing viral replication.
Article
Engineering, Biomedical
Ajjima Chansaenroj, Christabella Adine, Sawanya Charoenlappanit, Sittiruk Roytrakul, Ladawan Sariya, Thanaphum Osathanon, Sasitorn Rungarunlert, Ganokon Urkasemsin, Risa Chaisuparat, Supansa Yodmuang, Glauco R. Souza, Joao N. Ferreira
Summary: This study successfully generated three-dimensional cultures of SG functional organoids and hDPSC using the M3DB platform, and utilized EV for repairing SG epithelial damage. The EV derived from SGo were found to have more pronounced biological effects, such as stimulating epithelial growth, compared to those derived from hDPSC.
BIOACTIVE MATERIALS
(2022)
Review
Medicine, Research & Experimental
Fengjiao Li, Peng Zhang, Saizhi Wu, Lianwen Yuan, Zhonghua Liu
Summary: Organoids are three-dimensional structures developed from adult stem cells, embryonic stem cells, and pluripotent stem cells through a self-organization process, exhibiting functionalities and features similar to those of in vivo organs. Researchers have established various human tissue-derived epithelial organoids using organoid culture techniques, showing strong research and application prospects in drug discovery, personalized drug response testing, disease mechanism research, and regenerative medicine.
MOLECULAR PHARMACEUTICS
(2021)
Article
Cell Biology
Sylvia C. Hewitt, San-Pin Wu, Tianyuan Wang, Steven L. Young, Thomas E. Spencer, Francesco J. DeMayo
Summary: The study demonstrates that uterine cells respond to estrogen and progesterone through their nuclear receptors ESR1 and PGR, with the involvement of chromatin structures. The organoids model provides insights into the regulatory mechanisms of hormone responsiveness.
Review
Gastroenterology & Hepatology
Marta B. Afonso, Vanda Marques, Saskia W. C. van Mil, Cecilia M. P. Rodrigues
Summary: In the last decade, research has seen a revolutionary development with the creation of mini human livers in a dish. These liver organoids, derived from self-organizing stem cells, closely resemble native livers in terms of composition, architecture, and function. The use of liver organoids has the potential to overcome previous challenges in studying the human liver, allowing for better modeling of liver diseases, drug testing, and bioengineering advancements.
Article
Cell & Tissue Engineering
Sang Yun Jeong, Woo Hee Choi, Seong Gyeong Jeon, Sookon Lee, Jong-Moon Park, Mira Park, Hookeun Lee, Helen Lew, Jongman Yoo
Summary: The study demonstrates that the established LG organoids resemble the characteristics of normal LG tissue and may be used as a therapy for patients with DED.
STEM CELL RESEARCH & THERAPY
(2021)
Review
Medical Laboratory Technology
Enrique Podaza, Hui-Hsuan Kuo, John Nguyen, Olivier Elemento, M. Laura Martin
Summary: Patient-derived tumor organoids (PDTOs) have emerged as pre-clinical models that preserve the mutational landscape and tumor-clonal heterogeneity of primary tumors. However, they have limitations as they lose the components of the tumor microenvironment during their establishment. This review addresses the effects of different components of the tumor microenvironment on tumor behavior and treatment response, as well as strategies to improve the value of PDTOs through culture and co-culture techniques.
TRANSLATIONAL RESEARCH
(2022)
Review
Immunology
Nathan Provin, Matthieu Giraud
Summary: The thymus plays a crucial role in immune tolerance, but genetic disorders can lead to thymic dysfunction and autoimmune syndromes. Recent advances in gene editing and pluripotent stem cell differentiation offer new possibilities for studying and treating genetic pathologies affecting the thymus.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Cell Biology
Hui Sun, Yi-Xuan Zhang, Yu-Mei Li
Summary: Current human skin substitutes lack important skin appendages and cells, highlighting the need for improvement; skin organoids generated from stem cells are expected to possess the complexity and function of natural skin.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Reproductive Biology
Riley E. Thompson, Mindy A. Meyers, Christopher Premanandan, Fiona K. Hollinshead
Summary: Next-generation in vitro culture models are required to study reproductive pathologies in domestic animals. Organoids, a physiologically representative 3D cell culture system, combined with cryopreservation, can provide a long-term experimental model bypassing seasonality and reproductive tract availability restrictions. This study reports the generation and cryopreservation of feline oviductal organoids for the first time. The availability of cryopreserved feline oviductal organoids may positively influence in vitro gamete and embryo development, embryo quality, and pregnancy rates, especially in endangered felid breeding programs.
Article
Biology
Xin-Yao Sun, Xiang-Chun Ju, Yang Li, Peng-Ming Zeng, Jian Wu, Ying-Ying Zhou, Li-Bing Shen, Jian Dong, Yue-Jun Chen, Zhen-Ge Luo
Summary: This study successfully fused blood vessels and brain organoids to obtain vascularized brain organoids. The fused organoids not only had vascular network-like structures and increased number of neural progenitors, but also contained functional blood-brain barrier-like structures and microglial cells with immune functions.
Article
Computer Science, Interdisciplinary Applications
Lucia Hradecka, David Wiesner, Jakub Sumbal, Zuzana Sumbalova Koledova, Martin Maska
Summary: We introduce an automated and deep-learning-based workflow for quantitatively analyzing the spatiotemporal development of mammary epithelial organoids in 2D+t sequences. This workflow incorporates a convolutional neural network (U-Net) trained with computer-generated bioimage data, adaptive morphological filtering, and a shape-similarity-constrained tracking procedure to reliably identify and track organoid instances of interest.
IEEE TRANSACTIONS ON MEDICAL IMAGING
(2023)
Article
Cell Biology
Byung Ho Lee, Irene Seijo-Barandiaran, Anne Grapin-Botton
Summary: Epithelial organoids can mimic morphogenetic processes in vivo, such as lumen and multilayer formation, folding, branching, delamination, and elongation. This article elaborates on the signaling molecules controlling morphogenesis, including their emergence as signaling centers in the organoids. It also discusses how mechanical cues and environmental material properties influence organoid shape.
CURRENT OPINION IN GENETICS & DEVELOPMENT
(2022)
Article
Multidisciplinary Sciences
Shuting Liu, Kangjian Xiang, Fa Yuan, Mengqing Xiang
Summary: Recently, mouse fibroblasts have been successfully reprogrammed into self-organized and networked induced autonomic ganglion (iAG) organoids, using a combination of transcription factors Ascl1, Phox2a/b, and Hand2. The iAG neurons exhibit molecular properties, subtype diversity, and electrophysiological characteristics of autonomic neurons. They can also integrate into the superior cervical ganglia and innervate and control the beating rate of co-cultured ventricular myocytes. Therefore, iAG organoids can be valuable tools for studying autonomic nervous system diseases, drug screening, and cell-based therapies.
Correction
Biochemistry & Molecular Biology
Therese Seidlitz, Bon-Kyoung Koo, Daniel E. Stange
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Gastroenterology & Hepatology
Wenjie Ge, Algera Goga, Yuliang He, Pamuditha N. Silva, Christian Kurt Hirt, Karolin Herrmanns, Ilaria Guccini, Svenja Godbersen, Gerald Schwank, Markus Stoffel
Summary: miR-802 is a highly abundant and acinar-enriched pancreatic miRNA that is silenced during early stages of injury or oncogenic Kras(G12D)-induced transformation. Genetic ablation of mir-802 cooperates with Kras(G12D) by promoting ADM formation. miR-802 deficiency results in de-repression of the miR-802 targets Arhgef12, RhoA, and Sdc4, activation of RhoA, and induction of the downstream RhoA effectors ROCK1, LIMK1, COFILIN1, and EZRIN, thereby increasing F-actin rearrangement.
Article
Multidisciplinary Sciences
German Belenguer, Gianmarco Mastrogiovanni, Clare Pacini, Zoe Hall, Anna M. Dowbaj, Robert Arnes-Benito, Aleksandra Sljukic, Nicole Prior, Sofia Kakava, Charles R. Bradshaw, Susan Davies, Michele Vacca, Kourosh Saeb-Parsy, Bon-Kyoung Koo, Meritxell Huch
Summary: RNF43/ZNRF3 alterations contribute to liver disease and liver cancer by affecting differentiation and lipid metabolism of hepatocytes. The loss of these genes leads to steatohepatitis and an increase in unsaturated lipids. Deletion of Rnf43/Znrf3 results in defective hepatocyte regeneration and liver cancer, causing an imbalance between differentiation and proliferation. Interestingly, ZNRF3 mutant liver cancer patients have a poorer prognosis and exhibit altered hepatic lipid metabolism and steatohepatitis/NASH signatures.
NATURE COMMUNICATIONS
(2022)
Article
Cell & Tissue Engineering
Chanyi Lu, Xiaoli Lin, Jumpei Yamashita, Ranhui Xi, Minliang Zhou, Yali Zhang, Hong Wang, Robert E. Margolskee, Bon-Kyoung Koo, Hans Clevers, Ichiro Matsumoto, Peihua Jiang
Summary: The study reveals the important roles of RNF43/ZNRF3 in regulating taste and lingual epithelial tissue homeostasis. R-spondin interacts with RNF43/ZNRF3 to enhance WNT signaling, thereby controlling taste cell regeneration and lingual epithelial tissue homeostasis.
Article
Chemistry, Multidisciplinary
Soon-Chan Kim, Ji Won Park, Ha-Young Seo, Minjung Kim, Jae-Hyeon Park, Ga-Hye Kim, Ja Oh Lee, Young-Kyoung Shin, Jeong Mo Bae, Bon-Kyoung Koo, Seung-Yong Jeong, Ja-Lok Ku
Summary: The study reveals the widespread subregional heterogeneity within single tumors, leading to varied drug responses, emphasizing the importance of understanding the molecular heterogeneity of each tumor and targeting common somatic driver mutations positioned in all tumor subregional clones.
Article
Medicine, Research & Experimental
Anne E. J. Hillen, Martina Hruzova, Tanja Rothgangl, Marjolein Breur, Marianna Bugiani, Marjo S. van der Knaap, Gerald Schwank, Vivi M. Heine
Summary: This study tested a dual-AAV approach for gene therapy in VWM mice using CRISPR/Cas9, but found that the DNA repair induced by CRISPR/Cas9 was mainly insertion or deletion mutations, which did not lead to sufficient correction of the VWM variant. Moreover, the indel formation in Eif2b5 may cause additional issues, suggesting that other gene editing technologies like base- or prime editing might be better suited for VWM correction.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Cell Biology
Desiree Boeck, Tanja Rothgangl, Lukas Villiger, Lukas Schmidheini, Mai Matsushita, Nicolas Mathis, Eleonora Ioannidi, Nicole Rimann, Hiu Man Grisch-Chan, Susanne Kreutzer, Zacharias Kontarakis, Manfred Kopf, Beat Thoeny, Gerald Schwank
Summary: Prime editing is a highly versatile CRISPR-based technology that is able to edit genomes without causing DNA double-strand breaks. In this study, the researchers developed a smaller version of the SpCas9 prime editor and used a viral delivery system to edit genes in the liver. They were able to successfully correct a disease-causing mutation in a mouse model of phenylketonuria, leading to therapeutic reduction of phenylalanine in the blood. Although there are limitations to the current approach, further development of the technology may offer potential treatments for genetic liver diseases.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Nina Frey, Luigi Tortola, David Egli, Sharan Janjuha, Tanja Rothgangl, Kim Fabiano Marquart, Franziska Ampenberger, Manfred Kopf, Gerald Schwank
Summary: This study systematically explores the immune evasion mechanisms of pancreatic ductal adenocarcinoma (PDA) and identifies Vps4b and Rnf31 as essential factors for escaping CD8(+) T cell killing. Inactivation of Vps4b impairs autophagy, leading to increased accumulation of granzyme B derived from CD8(+) T cells and subsequent tumor cell lysis. Inactivation of Rnf31 protects tumor cells from TNF-mediated caspase 8 cleavage and apoptosis induction. Transplantation of Vps4b- or Rnf31-deficient pancreatic tumors into immune competent mice shows increased CD8(+) T cell infiltration and effector function, as well as significantly reduced tumor growth.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Yusuke Yoshimatsu, Tomohisa Sujino, Kentaro Miyamoto, Yosuke Harada, Shun Tanemoto, Keiko Ono, Satoko Umeda, Kosuke Yoshida, Toshiaki Teratani, Takahiro Suzuki, Yohei Mikami, Nobuhiro Nakamoto, Nobuo Sasaki, Kaoru Takabayashi, Naoki Hosoe, Haruhiko Ogata, Kazuaki Sawada, Takeshi Imamura, Akihiko Yoshimura, Takanori Kanai
Summary: CD4(+) Foxp3(+) regulatory T cells (Tregs) play a crucial role in the homeostasis of the colon, but the mechanism controlling their localization is still unclear. This study demonstrates that indigo naturalis (IN), an aryl hydrocarbon receptor (AhR) agonist, increases the numbers of Helios+ Tregs and MHC class II+ epithelial cells (ECs) in the colon. Additionally, IN treatment leads to an increase in CD25(+) T cells near the surface of ECs in ulcerative colitis (UC) patients compared to other therapies.
Article
Medicine, Research & Experimental
Therese Seidlitz, Tim Schmaeche, Fernando Garcia, Joon Ho Lee, Nan Qin, Susan Kochall, Juliane Fohgrub, David Pauck, Alexander Rothe, Bon-Kyoung Koo, Juergen Weitz, Marc Remke, Javier Munoz, Daniel E. Stange
Summary: This study generated three murine organoid models to investigate the impact of different pathway alterations on gastric cancer. It identified a potential treatment approach for gastric cancer patients with RTK/MAPK pathway alterations, suggesting their susceptibility to HDAC inhibition.
EMBO MOLECULAR MEDICINE
(2022)
Article
Biotechnology & Applied Microbiology
Nicolas Mathis, Ahmed Allam, Lucas Kissling, Kim Fabiano Marquart, Lukas Schmidheini, Cristina Solari, Zsolt Balazs, Michael Krauthammer, Gerald Schwank
Summary: This study conducted a high-throughput screen to identify sequence context features that influence prime editing outcomes. They trained a neural network called PRIDICT, which reliably predicts editing rates for various genetic changes. The validation results showed that PRIDICT can significantly increase prime editing efficiencies in different cell types.
NATURE BIOTECHNOLOGY
(2023)
Article
Developmental Biology
Bianca Dietrich, Victoria Kunihs, Andreas I. Lackner, Gudrun Meinhardt, Bon-Kyoung Koo, Jurgen Pollheimer, Sandra Haider, Martin Knoefler
Summary: This study reveals that autocrine NOTCH3 signaling controls human placental development by promoting self-renewal of cytotrophoblast progenitors.
Article
Biochemistry & Molecular Biology
Lukas Schmidheini, Nicolas Mathis, Kim Fabiano Marquart, Tanja Rothgangl, Lucas Kissling, Desiree Bock, Christelle Chanez, Jingrui Priscilla Wang, Martin Jinek, Gerald Schwank
Summary: CRISPR-Cas9 genome engineering is a powerful technology for correcting genetic diseases. In this study, researchers used phage-assisted continuous directed evolution to expand the PAM compatibility of CjCas9, resulting in a new variant called evoCjCas9. This variant can recognize a broader range of PAM sequences and has higher nuclease activity.
NATURE CHEMICAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Gabriele Colozza, So-Yeon Park, Bon-Kyoung Koo
Summary: Tumors gain a competitive edge over intestinal stem cells by exploiting the self-renewal processes of the stem cells. The dynamics of stem cells in the intestines are regulated by a network of molecular signals and competition for limited space. The Wnt signaling pathway and its inhibitors play a crucial role in maintaining the balance between self-renewal and differentiation. Intestinal cancer cells bypass these regulatory mechanisms, allowing them to outcompete normal cells.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)
Review
Cell & Tissue Engineering
Jihoon Kim, Bon-Kyoung Koo, Hans Clevers
Summary: The COVID-19 pandemic caused significant disruptions in human life, but through the use of technologies such as organoid models, we have been able to gain a better understanding of the virus and develop strategies to combat the disease.
INTERNATIONAL JOURNAL OF STEM CELLS
(2022)
