Review
Biochemistry & Molecular Biology
Silvia De Siervi, Cristian Turato
Summary: Primary liver cancers are a major cause of cancer-related death worldwide. Three-dimensional liver organoids provide innovative models for studying the pathological mechanisms of tumors and have potential applications in regenerative medicine and drug discovery. This review discusses the current advances in liver organoids, including development protocols and possible applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Saade Abdalkareem Jasim, Dmitry Olegovich Bokov, Wanich Suksatan, Fahad Alsaikhan, Mohammed Abed Jawad, Satish Kumar Sharma, Supat Chupradit, Lakshmi Thangavelu
Summary: We are currently in the midst of a revolution in regenerative medicine, with recent advancements in organoid technology offering new possibilities for the study of human biology and diseases. Organoid models have completely transformed the field of in vitro culture tools for biomedical research by accurately replicating the cellular heterogeneity, structure, and functions of primary tissues. This technology allows researchers to recreate human organs and disease models in a laboratory setting, holding great promise for applications in regenerative medicine, drug discovery, and precision medicine.
CURRENT MEDICINAL CHEMISTRY
(2023)
Article
Cell & Tissue Engineering
Wenyue Shen, An Shao, Wuyuan Zhou, Lixia Lou, Andrzej Grzybowski, Kai Jin, Juan Ye
Summary: The purpose of this study is to explore the hotspots and future directions of retinal organoids (ROs), as well as to better understand the fields of greatest research opportunities. Through bibliometric analysis, it was found that the number of RO-related publications has rapidly increased, with the United States being the most prominent research country. Investigative Ophthalmology & Visual Science is the most productive journal in this field. Majlinda Lako has contributed the most research articles, while Olivier Goureau has the strongest collaborative work. The research can be divided into four keyword clusters: culture and differentiation, morphogenesis and modeling, gene therapy, and transplantation and visual restoration. The past decade has witnessed significant progress in the field of ROs, which is a young and promising research area. More attention should be paid to RO-related models and therapies for specific retinal diseases, especially inherited retinopathies.
CELL TRANSPLANTATION
(2023)
Article
Endocrinology & Metabolism
Sylvia C. Hewitt, Mackenzie J. Dickson, Nicole Edwards, Kathleen Hampton, Stavros Garantziotis, Francesco J. Demayo
Summary: The establishment of in vitro models to study diseases in the female reproductive tract is crucial. This study developed a non-invasive method to isolate endometrial epithelial and stromal cells from menstrual fluid, which can enhance our knowledge of their roles in diseases.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Mariangela Scalise, Fabiola Marino, Luca Salerno, Eleonora Cianflone, Claudia Molinaro, Nadia Salerno, Antonella De Angelis, Giuseppe Viglietto, Konrad Urbanek, Daniele Torella
Summary: Organoids are tiny, self-organized, three-dimensional tissue cultures derived from stem cell differentiation, mimicking specific tissue structures in vitro with great potential for a variety of applications. By exploiting the ability of cells to re-aggregate and reconstruct original organ architecture, organoids have the ability to overcome limitations of traditional 2D cell cultures, showing high promise in cardiovascular research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Energy & Fuels
Antonio Marra, Massimo Santarelli, Davide Papurello
Summary: The main purpose of this study is to create and validate a model that approximates the temperature trend of a receiver installed in a concentrated solar plant. Two models were developed using the Monte Carlo method for ray tracing, with one setting the maximum reflectivity of the paraboloid and the other setting a reflectivity of 80%. The optical and thermal performance of the receiver were calculated and compared to the manufacturer's values, and the model was validated by comparing the obtained temperatures with those measured by thermocouples. The average error was found to be 7% and 2% for two random days in 2020.
INTERNATIONAL JOURNAL OF ENERGY RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Jie Zhang, Lei Wang, Qianqian Song, Mingbing Xiao, Jie Gao, Xiaolei Cao, Wenjie Zheng
Summary: Environmental and genetic factors contribute to cancer development, and organoid models are a useful tool for studying the mechanisms of oncogenesis and developing targeted therapies.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Review
Physiology
Qianglin Liu, Anqi Zeng, Zibo Liu, Chunjie Wu, Linjiang Song
Summary: The liver, as the largest internal organ, plays a crucial role in multiple physiological processes. Previous liver research was mainly conducted on animal models and cell lines, lacking in species variability and heritable material retention. Primary hepatocytes also struggle to maintain metabolic functions after in vitro expansion. With the global burden of liver diseases increasing, 3D in vitro liver models, known as liver organoids, are in high demand. Liver organoid generation relies on various initiation cells and eventually forms three-dimensional structures in the presence of cytokines. Liver organoids have shown promising applications in drug screening, disease modeling, and individualized medicine. This review summarizes the generation process and clinical applications of liver organoids, providing new perspectives for liver physiology and disease research.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Waqas Iqbal, Yaru Wang, Pingnan Sun, Xiaoling Zhou
Summary: Historically, biological research has relied on animal models, but species-specific differences limit their applicability to certain liver-related questions. The advent of 3D organoid technology allows for the recapitulation of human organ biology, aiding in the understanding of disease mechanisms and drug screening.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Dmitrii Shek, Dishen Chen, Scott A. Read, Golo Ahlenstiel
Summary: Liver cancer, predicted to be the third most lethal cancer worldwide by 2030, is primarily caused by obesity, chronic alcohol abuse or viral hepatitis, with alcohol and high fat diet promoting intestinal permeability. Understanding the mechanisms by which liver cancers initiate and progress is crucial, and organoid culture offers advantages for studying the role of the gut-liver axis in cancer initiation and progression.
Review
Biochemistry & Molecular Biology
Yu Wu, Sisi Peng, Richard H. Finnell, Yufang Zheng
Summary: The neural tube is a critical structure in embryonic development, essential for the central nervous system. Neural tube defects are severe congenital anomalies with complex pathogenesis, and research into the mechanisms is ongoing. Neural tube organoids offer a promising model system to study neural tube formation and defects.
Article
Chemistry, Analytical
Adem Ozcelik, Burcin Irem Abas, Omer Erdogan, Evrim Cevik, Ozge Cevik
Summary: In this study, simple and low-cost microfluidic devices were designed and fabricated to develop an organoid model for drug testing for renal cancers. The results showed that the standard renal cancer organoids made on a lab-on-a-chip system can be used to measure drug effects and tumor microenvironment responses.
Article
Chemistry, Multidisciplinary
Tingting Tao, Pengwei Deng, Yaqing Wang, Xu Zhang, Yaqiong Guo, Wenwen Chen, Jianhua Qin
Summary: A new microfluidic multi-organoid system has been developed to replicate the human liver-pancreatic islet axis in both normal and disease states, providing a unique platform for future research and drug development in Type 2 diabetes mellitus.
Review
Oncology
Peiyuan Mu, Shujuan Zhou, Tao Lv, Fan Xia, Lijun Shen, Juefeng Wan, Yaqi Wang, Hui Zhang, Sanjun Cai, Junjie Peng, Guoqiang Hua, Zhen Zhang
Summary: Immunotherapy is a rapidly developing therapeutic approach that has revolutionized cancer treatment and revitalized tumor immunology research. 3D in vitro models, which can maintain tumor cells in a near-native state, are emerging as powerful tools and have been widely applied in oncology research. The novel 3D culture methods, such as co-culture of organoids and immune cells, ALI culture, 3D-microfluidic culture, and 3D-bioprinting, offer new approaches for tumor immunology study and have applications in personalized treatment, immunotherapy optimization, and adoptive cell therapy. This review introduces commonly used 3D in vitro models and summarizes their applications in different aspects of tumor immunology research. A preliminary analysis of the current shortcomings of these models and the outlook of future development is also provided.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Review
Pharmacology & Pharmacy
Anastasia Brooks, Xiaowen Liang, Yonglong Zhang, Chun-Xia Zhao, Michael S. Roberts, Haolu Wang, Lei Zhang, Darrell H. G. Crawford
Summary: Liver organoids, as self-organising and self-renewing models, provide a more physiologically relevant approach for disease modelling and personalized therapy. They are essential tools for testing drug efficacy and toxicity, facilitating drug validation and toxicity assessment.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Gastroenterology & Hepatology
Milena Armacki, Sandra Polaschek, Mareike Waldenmaier, Mareen Morawe, Claudia Ruhland, Rebecca Schmid, Andre Lechel, Umesh Tharehalli, Christoph Steup, Yasin Bektas, Hongxia Li, Johann M. Kraus, Hans A. Kestler, Stephan Kruger, Steffen Ormanns, Paul Walther, Tim Eiseler, Thomas Seufferlein
Correction
Genetics & Heredity
Aaheli Roy Choudhury, Zhenyu Ju, Meta W. Djojosubroto, Andrea Schienke, Andre Lechel, Sonja Schaetzlein, Hong Jiang, Anna Stepczynska, Chunfang Wang, Jan Buer, Han-Woong Lee, Thomas von Zglinicki, Arnold Ganser, Peter Schirmacher, Hiromitsu Nakauchi, K. Lenhard Rudolph
Editorial Material
Gastroenterology & Hepatology
Sabine Colnot, Andre Lechel
JOURNAL OF HEPATOLOGY
(2020)
Review
Oncology
Lena in der Stroth, Umesh Tharehalli, Cagatay Guenes, Andre Lechel
Article
Gastroenterology & Hepatology
Johann Gout, Lukas Perkhofer, Mareen Morawe, Frank Arnold, Michaela Ihle, Stephanie Biber, Sebastian Lange, Elodie Roger, Johann M. Kraus, Katja Stifter, Stephan A. Hahn, Andrea Zamperone, Thomas Engleitner, Martin Mueller, Karolin Walter, Eva Rodriguez-Aznar, Bruno Sainz Jr, Patrick C. Hermann, Elisabeth Hessmann, Sebastian Mueller, Ninel Azoitei, Andre Lechel, Stefan Liebau, Martin Wagner, Diane M. Simeone, Hans A. Kestler, Thomas Seufferlein, Lisa Wiesmueller, Roland Rad, Pierre-Olivier Frappart, Alexander Kleger
Summary: The study identified synergistic effects in inhibiting PARP, ATR, and DNA-PKcs that lead to synthetic lethality in ATM-deficient pancreatic ductal adenocarcinoma. Chemical inhibition of ATM sensitized human PDAC cells towards this combinatorial therapy, which was also found to overcome PARP inhibitor resistance. These findings suggest potential mutation-specific therapeutic strategies that may be applied through ATM inhibition regardless of genotype.
Article
Oncology
Katja Stifter, Jana Krieger, Leonie Ruths, Johann Gout, Medhanie Mulaw, Andre Lechel, Alexander Kleger, Thomas Seufferlein, Martin Wagner, Reinhold Schirmbeck
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2020)
Article
Gastroenterology & Hepatology
Laura Elisa Buitrago-Molina, Silke Marhenke, Diana Becker, Robert Geffers, Timo Itzel, Andreas Teufel, Hartmut Jaeschke, Andre Lechel, Kristian Unger, Jovana Markovic, Amar Deep Sharma, Jens U. Marquardt, Michael Saborowski, Anna Saborowski, Arndt Vogel
Summary: The study found that loss of p53 in a model of metabolic liver injury impairs the oxidative stress response, aggravates liver damage, and shows a complex interdependency between p21 and p53.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Oncology
Frank Arnold, Johann Gout, Heike Wiese, Stephanie E. Weissinger, Elodie Roger, Lukas Perkhofer, Karolin Walter, Jeanette Scheible, Caterina Prelli Bozzo, Andre Lechel, Thomas J. Ettrich, Ninel Azoitei, Li Hao, Axel Fuerstberger, Ewa K. Kaminska, Konstantin M. J. Sparrer, Volker Rasche, Sebastian Wiese, Hans A. Kestler, Peter Moller, Thomas Seufferlein, Pierre-Olivier Frappart, Alexander Kleger
Summary: Research has identified RINT1 as a crucial mediator of cellular homeostasis in PDAC, with its depletion potentially affecting the fate of PDAC cells. The study found that RINTI directly correlates with survival in patients with PDAC by disturbing the SUMOylation process, indicating a potential new therapeutic approach for this aggressive cancer.
Correction
Cell Biology
Tobias Sperka, Zhangfa Song, Yohei Morita, Kodandaramireddy Nalapareddy, Luis Miguel Guachalla, Andre Lechel, Yvonne Begus-Nahrmann, Martin D. Burkhalter, Monika Mach, Falk Schlaudraff, Birgit Liss, Zhenyu Ju, Michael R. Speicher, K. Lenhard Rudolph
Summary: A correction to this paper has been published, please refer to the link for details.
NATURE CELL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Rossana Paganoni, Andre Lechel, Maja Vujic Spasic
Summary: Liver cancer is a rapidly growing health issue globally, with iron identified as a potential risk factor for hepatocellular carcinoma. Tight regulation of cellular and systemic iron levels is essential in preventing or delaying the progression of liver cancer. Various metabolic disorders, such as hereditary hemochromatosis, non-alcoholic fatty liver disease, obesity, and type 2 diabetes, have been associated with increased susceptibility to hepatocellular carcinoma in the context of dysregulated iron metabolism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Frank Arnold, Pallavi U. Mahaddalkar, Johann M. Kraus, Xiaowei Zhong, Wendy Bergmann, Dharini Srinivasan, Johann Gout, Elodie Roger, Alica K. Beutel, Eugen Zizer, Umesh Tharehalli, Nora Daiss, Ronan Russell, Lukas Perkhofer, Rupert Oellinger, Qiong Lin, Ninel Azoitei, Frank-Ulrich Weiss, Markus M. Lerch, Stefan Liebau, Sarah-Fee Katz, Andre Lechel, Roland Rad, Thomas Seufferlein, Hans A. Kestler, Michael Ott, Amar Deep Sharma, Patrick C. Hermann, Alexander Kleger
Summary: The study reveals DKK3 as a key regulator of organ regeneration by affecting generation and proliferation of stem cells. The expression levels of DKK3 are elevated in both animals and human patients upon injury. Knockout of DKK3 can reduce liver damage and accelerate recovery from pancreatitis.
Article
Oncology
Julia Maier, Andre Lechel, Ralf Marienfeld, Thomas F. E. Barth, Peter Moeller, Kevin Mellert
Summary: This study reports high levels of mRNA and protein expression of CARD9 in the RS cell line U-RT1. Co-immunoprecipitation revealed the assembly of a CBM complex using CARD9 instead of CARD11. Western blot analyses showed phosphorylation of IκB and IKK in U-RT1, indicating a constitutively active canonical NF-kB pathway. Knockdown of CARD9 resulted in a significant reduction in cell viability and CYLD cleavage products. Immunostaining for CARD9 was also observed in 53% of RS tissue specimen cases analyzed. This is the first report on the ectopic expression and function of CARD9 in an aggressive B-cell lymphoma, suggesting that CARD9 may contribute to the pathogenesis of RS.
Article
Gastroenterology & Hepatology
Willemien van Zwol, Antoine Rimbert, Justina C. Wolters, Marieke Smit, Vincent W. Bloks, Niels J. Kloosterhuis, Nicolette C. A. Huijkman, Mirjam H. Koster, Umesh Tharehalli, Simon M. de Neck, Colin Bournez, Marceline M. Fuh, Jeroen Kuipers, Sujith Rajan, Alain de Bruin, Henry N. Ginsberg, Gerard J. P. van Westen, M. Mahmood Hussain, Ludger Scheja, Joerg Heeren, Philip Zimmerman, Bart van de Sluis, Jan Albert Kuivenhoven
Summary: By analyzing the co-expression of genes, we identified the small leucine-rich protein 1 (SMLR1) as a player in the VLDL biogenesis pathway. The loss of hepatic SMLR1 in mice leads to hepatic steatosis, reduced VLDL secretion, providing protection against hyperlipidemia and atherosclerosis.
Correction
Gastroenterology & Hepatology
P. O. Frappart, K. Walter, J. Gout, A. K. Beutel, M. Morawe, F. Arnold, M. Breunig, T. F. Barth, R. Marienfeld, L. Schulte, T. Ettrich, T. Hackert, M. Svinarenko, R. Rosler, S. Wiese, H. Wiese, L. Perkhofer, M. Mueller, A. Lechel, B. Sainz, P. C. Hermann, T. Seufferlein, A. Kleger
UNITED EUROPEAN GASTROENTEROLOGY JOURNAL
(2020)