Article
Multidisciplinary Sciences
Mariana A. Branco, Tiago P. Dias, Joaquim M. S. Cabral, Perpetua Pinto-do-O, Maria Margarida Diogo
Summary: In this study, a self-organized human multilineage organoid was developed to recreate the co-emergence of pro-epicardium, septum transversum mesenchyme, and liver bud. The impact of WNT, BMP, and retinoic acid signaling modulation on the specification of multilineage organoids was investigated. Co-culturing these organoids with cardiomyocyte aggregates resulted in the generation of a self-organized heart organoid with an epicardium-like layer surrounding a myocardium-like tissue. These heart organoids recapitulates the impact of epicardial cells on promoting cardiomyocyte proliferation and maturation. This study provides valuable insights into the myocardium-epicardium interaction during heart organogenesis in both healthy and diseased settings.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Nur Yucer, Rodney Ahdoot, Michael J. Workman, Alexander H. Laperle, Maria S. Recouvreux, Kathleen Kurowski, Diana J. Naboulsi, Victoria Liang, Ying Qu, Jasmine T. Plummer, Simon A. Gayther, Sandra Orsulic, Beth Y. Karlan, Clive N. Svendsen
Summary: Germline pathogenic mutations in BRCA1 genes drive normal fallopian tube epithelial cell transformation to high-grade serous ovarian cancer. Induced pluripotent stem cells from individuals with these mutations show neoplastic transformation when differentiated into FTE organoids, indicating a potential value in predicting clinical severity prior to disease onset. This platform can be used for personalized mechanistic and drug screening studies.
Article
Biology
Mychel R. P. T. Morais, Pinyuan Tian, Craig Lawless, Syed Murtuza-Baker, Louise Hopkinson, Steven Woods, Aleksandr Mironov, David A. Long, Daniel P. Gale, Telma M. T. Zorn, Susan J. Kimber, Roy Zent, Rachel Lennon
Summary: By studying kidney organoids, we have revealed the complex and dynamic nature of basement membrane assembly, and identified its importance in human development and disease.
Article
Biochemistry & Molecular Biology
Xinyu Chen, Hexige Saiyin, Yang Liu, Yuqi Wang, Xuan Li, Rong Ji, Lixiang Ma
Summary: Researchers have developed a method to construct human striatal organoids using human pluripotent stem cells, which partially replicate the fetal striatum and can be used to study striatal development, striatum-related disorders, and neural circuitry between different brain regions.
Article
Cell & Tissue Engineering
Xiaoyu Zhao, Cun Li, Xiaojuan Liu, Man Chun Chiu, Dong Wang, Yuxuan Wei, Hin Chu, Jian-Piao Cai, Ivy Hau-Yee Chan, Kenneth Kak-Yuen Wong, Jasper Fuk-Woo Chan, Kelvin Kai-Wang To, Kwok Yung Yuen, Jie Zhou
Summary: Optimized human intestinal organoids can better simulate enterovirus and coronavirus infections, with significantly more susceptibility to EV-A71 than CVA16. The dynamics of virus-host interaction differ between SARS-CoV and SARS-CoV-2, with SARS-CoV triggering minimal cellular response and SARS-CoV-2 eliciting a moderate cellular response, shedding light on the distinct pathogenicity of these viral pathogens.
Article
Genetics & Heredity
Alise Zagare, Kyriaki Barmpa, Semra Smajic, Lisa M. Smits, Kamil Grzyb, Anne Grunewald, Alexander Skupin, Sarah L. Nickels, Jens C. Schwamborn
Summary: Human brain organoids are a valuable tool for studying neurodegenerative diseases like Parkinson's disease. This study shows that the in vitro model of human midbrain organoids accurately recapitulates the developmental path and cellular composition of the in vivo midbrain. The researchers also discovered that a specific genetic variant affects neurodevelopment and identified potential candidate genes associated with this variant.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Biotechnology & Applied Microbiology
Min Shi, Kyle W. McCracken, Ankit B. Patel, Weitao Zhang, Lioba Ester, M. Todd Valerius, Joseph Bonventre
Summary: This study describes a highly efficient method for differentiating human pluripotent stem cells into kidney collecting duct cells. The process involves inducing the stem cells into progenitor cells, forming organoids with similar morphology to fetal kidney, and ultimately differentiating into functional collecting duct cells.
NATURE BIOTECHNOLOGY
(2023)
Article
Neurosciences
Hang Yao, Daisy Hu, Juan Wang, Wei Wu, Helen H. Zhao, Lu Wang, Joe Gleeson, Gabriel G. Haddad
Summary: Buprenorphine (BUP) was found to mitigate the methadone (MTD)-induced growth restriction during neurodevelopment and showed less suppressive effects on neural network communications due to its κ-receptor antagonism and lack of NMDA antagonism.
Article
Chemistry, Multidisciplinary
Meng Huang, Shao Xu, Yuzhe Li, Li Shang, Xiudan Zhan, Chaoyin Qin, Jun Su, Zijin Zhao, Yi He, Lina Qin, Wei Zhao, Wenyong Long, Qing Liu
Summary: High-grade meningioma has a limited response to surgery and postoperative radiotherapy, and the factors that drive its malignancy and recurrence are largely unknown. This study used scRNA-Seq to identify a unique initiating cell subpopulation (SULT1E1(+)) in high-grade meningiomas, and found that it modulates the polarization of M2-type macrophages, promoting meningioma progression and recurrence. A novel patient-derived meningioma organoid (MO) model was also established, which fully retained the aggressiveness of SULT1E1(+) and showed invasiveness in the brain after orthotopic transplantation. Targeting SULT1E1(+) in MOs identified the synthetic compound SRT1720 as a potential agent for systemic treatment and radiation sensitization.
Article
Engineering, Biomedical
Min Beom Kim, Soonho Hwangbo, Sungho Jang, Yun Kee Jo
Summary: The recent increase in complex physiological host-microbe interactions has led to a demand for in vitro models that replicate the microbial microenvironment in the human body. Organoids, an in vitro culture system that closely mimics the structure, function, and genetic features of human organs, are emerging as a promising tool for studying host-microbe interactions. Co-cultures of organoids with microbes show great potential in simulating complex host-microbe interactions and advancing related fields. This review provides an overview of bioengineering approaches for microbe-co-cultured organoids and highlights the latest developments in their applications for studying human physiology and pathophysiology.
MATERIALS TODAY BIO
(2022)
Article
Multidisciplinary Sciences
Samaneh K. Sarvestani, Steven Signs, Bo Hu, Yunku Yeu, Hao Feng, Ying Ni, David R. Hill, Robert C. Fisher, Sylvain Ferrandon, Reece K. DeHaan, Jennifer Stiene, Michael Cruise, Tae Hyun Hwang, Xiling Shen, Jason R. Spence, Emina H. Huang
Summary: This study successfully developed an induced human UC-derived organoid (iHUCO) model using induced pluripotent stem cells (iPSCs) to recapitulate disease histological and functional features, and confirmed the role of CXCL8/CXCR1 in the pathogenesis of UC.
NATURE COMMUNICATIONS
(2021)
Article
Biochemical Research Methods
Lika Drakhlis, Santoshi Biswanath Devadas, Robert Zweigerdt
Summary: The research demonstrates a feasible protocol for directing human pluripotent stem cell aggregates to differentiate into heart-forming organoids using chemical modulators of the WNT pathway. This protocol, involving preculture and chemical induction steps, efficiently generates HFOs, offering a new tool for cell studies and drug development.
Article
Microbiology
Man Chun Chiu, Cun Li, Xiaojuan Liu, Wenjun Song, Zhixin Wan, Yifei Yu, Jingjing Huang, Ding Xiao, Hin Chu, Jian-Piao Cai, Kelvin Kai-Wang To, Kwok Yung Yuen, Jie Zhou
Summary: This article reports on an organoid culture system of the nasal epithelium, which is essential for understanding cell biology and virus-host interaction in the human upper respiratory tract. The system allows for efficient reconstruction and stable expansion of the human nasal epithelium, providing a convenient and robust tool for studying SARS-CoV-2 infection and assessing the infectivity of emerging variants.
Review
Biochemistry & Molecular Biology
Nina S. Corsini, Juergen A. Knoblich
Summary: For a long time, animal models have been the primary means of gaining insight into the fundamental principles of human biology and disease. However, due to species differences, some developmental and disease mechanisms have been challenging to study. The advent of organoid technology over a decade ago has provided a new model system to investigate human-specific aspects of biology. The use of human 3D organoids, along with advancements in single-cell technologies, has revealed unprecedented insights into human biology and disease mechanisms.
Article
Medicine, Research & Experimental
Chiara Lago, Aniello Federico, Gloria Leva, Norman L. Mack, Benjamin Schwalm, Claudio Ballabio, Matteo Gianesello, Luana Abballe, Isabella Giovannoni, Sofia Reddel, Sabrina Rossi, Nicolas Leone, Andrea Carai, Angela Mastronuzzi, Alessandra Bisio, Alessia Soldano, Concetta Quintarelli, Franco Locatelli, Marcel Kool, Evelina Miele, Luca Tiberi
Summary: This study presents a protocol for efficient generation, expansion, and biobanking of pediatric brain cancer organoids. These organoids recapitulate histological features, DNA methylation profiles, and intratumor heterogeneity of the tumors. The study also shows that the organoids respond similarly to the same therapeutic regimens as the patients. These findings highlight the potential of organoids for research and personalized medicine.
EMBO MOLECULAR MEDICINE
(2023)
Article
Cell & Tissue Engineering
Felix Manstein, Kevin Ullmann, Christina Kropp, Caroline Halloin, Wiebke Triebert, Annika Franke, Clara-Milena Farr, Anais Sahabian, Alexandra Haase, Yannik Breitkreuz, Michael Peitz, Oliver Brustle, Stefan Kalies, Ulrich Martin, Ruth Olmer, Robert Zweigerdt
Summary: By combining STBR technology with in silico process modeling, challenges in hPSC production were overcome, leading to a rapid 70-fold increase in cell expansion and maintenance of cell quality stability.
STEM CELLS TRANSLATIONAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Andre Cronemberger Andrade, Martin Wolf, Heide-Marie Binder, Fausto Gueths Gomes, Felix Manstein, Patricia Ebner-Peking, Rodolphe Poupardin, Robert Zweigerdt, Katharina Schallmoser, Dirk Strunk
Summary: The study found that the quantity of iPSC-EVs is influenced by oxygen conditions and the method of EV preparation, with the best recovery observed at 1% oxygen and significantly elevated angiogenic potential.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell & Tissue Engineering
Alexandra Haase, Tim Kohrn, Veronika Fricke, Maria Elena Ricci Signorini, Merlin Witte, Gudrun Goehring, Ina Gruh, Ulrich Martin
Summary: This article describes a transgenic hiPSC line with dual reporter genes, which can be used to monitor engraftment, calcium fluctuations, and coupling of iPSC derivatives such as cardiomyocytes.
STEM CELL RESEARCH
(2021)
Article
Cell & Tissue Engineering
S. Merkert, S. Wunderlich, J. Beier, A. Franke, K. Schwanke, G. Gohring, T. Kraft, A. Francino, R. Zweigerdt, U. Martin
Summary: The study generated two iPSC clones from a HCM patient, heterozygous for the p.Arg723Gly mutation in the MYH7 gene, which could be valuable for investigating the pathogenesis of HCM.
STEM CELL RESEARCH
(2021)
Correction
Biotechnology & Applied Microbiology
Lika Drakhlis, Santoshi Biswanath, Clara-Milena Farr, Victoria Lupanow, Jana Teske, Katharina Ritzenhoff, Annika Franke, Felix Manstein, Emiliano Bolesani, Henning Kempf, Simone Liebscher, Katja Schenke-Layland, Jan Hegermann, Lena Nolte, Heiko Meyer, Jeanne de la Roche, Stefan Thiemann, Christian Wahl-Schott, Ulrich Martin, Robert Zweigerdt
NATURE BIOTECHNOLOGY
(2021)
Article
Chemistry, Analytical
Michael Pflaum, Julia Dahlmann, Lena Engels, Hossein Naghilouy-Hidaji, Denise Adam, Janina Zoellner, Annette Otto, Sabrina Schmeckebier, Ulrich Martin, Axel Haverich, Ruth Olmer, Bettina Wiegmann
Summary: The study demonstrated the potential therapeutic effect of iPSC-derived endothelial cells (ECs) in forming a continuous, non-thrombogenic, and non-inflammatory monolayer on blood-contacting surfaces of biohybrid lung (BHL). These specific ECs could reduce platelet adhesion and repopulate scratched areas, showing promise for BHL application.
Article
Pharmacology & Pharmacy
Andras Polyak, Jens P. Bankstahl, Karen F. W. Besecke, Constantin Hozsa, Wiebke Triebert, Rajeswara Rao Pannem, Felix Manstein, Thomas Borcholte, Marcus Furch, Robert Zweigerdt, Robert K. Gieseler, Frank M. Bengel, Tobias L. Ross
Summary: This study optimized a method for the preparation of the highly lipophilic labeling synthon [Zr-89]Zr(oxinate)(4) for radiolabeling of liposomes and human induced pluripotent stem cells. The developed labeling protocol demonstrated high radiochemical yields and efficient cell internalization rates. Prolonged PET imaging confirmed the stability of labeled nanocarriers in vivo, emphasizing the potential of the method for drug delivery and cell therapy applications.
Article
Biochemical Research Methods
Mania Ackermann, Anna Rafiei Hashtchin, Felix Manstein, Marco Carvalho Oliveira, Henning Kempf, Robert Zweigerdt, Nico Lachmann
Summary: This study presents a detailed protocol for mass production of iPSC-derived macrophages in scalable suspension culture or in STBRs, allowing for stable generation of functional and highly pure macrophages. The technology enables real-time monitoring of crucial process parameters, promoting systematic process development, optimization, and linear upscaling.
Article
Biochemistry & Molecular Biology
Denisa Bojkova, Rui Costa, Philipp Reus, Marco Bechtel, Mark-Christian Jaboreck, Ruth Olmer, Ulrich Martin, Sandra Ciesek, Martin Michaelis, Jindrich Cinatl
Summary: SARS-CoV-2 infection induces a metabolic shift towards glycolysis in host cells, with the glycolysis inhibitor 2DG being developed for COVID-19 treatment. Enhanced levels of transketolase (TKT) in infected cells suggest a role for the non-oxidative PPP, supported by the TKT inhibitor BOT inhibiting SARS-CoV-2 replication and synergizing with 2DG. Metabolic drugs like BOT and 2DG may improve COVID-19 therapy outcomes by targeting both viral replication and immunopathology.
Article
Hematology
Anna Rafiei Hashtchin, Beate Fehlhaber, Miriam Hetzel, Felix Manstein, Jan Lennart Stalp, Silke Glage, Markus Abeln, Robert Zweigerdt, Antje Munder, Dorothee Viemann, Mania Ackermann, Nico Lachmann
Summary: Primary or secondary immunodeficiencies disrupt cellular and humoral immunity, leading to increased susceptibility to respiratory infections. Adoptive transfer of macrophages can enhance pulmonary immunity against Staphylococcus aureus, reducing bacterial load and tissue damage. Studies demonstrate that induced pluripotent stem cell-derived macrophages are more effective in combating S aureus infections compared to monocyte-derived macrophages.
Article
Multidisciplinary Sciences
Benedikt Jaeger, Jonas Christian Schupp, Linda Plappert, Oliver Terwolbeck, Gian Kayser, Peggy Engelhard, Taylor Sterling Adams, Robert Zweigerdt, Henning Kempf, Stefan Lienenklaus, Wiebke Garrels, Irina Nazarenko, Danny Jonigk, Malgorzata Wygrecka, Denise Klatt, Axel Schambach, Naftali Kaminski, Antje Prasse, Nataliia Artysh
Summary: This study focuses on the properties of airway basal cells (ABC) obtained from patients with idiopathic pulmonary fibrosis (IPF) and reveals the extensive reprogramming of IPF-ABC. The study also shows that IPF-ABC can induce fibroblast proliferation and extracellular matrix deposition in a 3D organoid model, and these changes can be reversed by SRC inhibition. The findings suggest that IPF-ABC and SRC inhibition may serve as potential targets for the treatment of IPF.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Laura von Schledorn, David Puertollano Martin, Nicole Cleve, Janina Zoellner, Doris Roth, Ben Ole Staar, Jan Hegermann, Felix C. Ringshausen, Janna Nawroth, Ulrich Martin, Ruth Olmer
Summary: Primary ciliary dyskinesia (PCD) is a rare genetic disorder that affects the function of motile cilia in the respiratory tract, leading to chronic inflammation and lung damage. Current treatment options for PCD are only symptomatic, highlighting the need for curative therapies. In this study, researchers developed an in vitro model using human induced pluripotent stem cells (hiPSC) to recapitulate the diseased phenotype of PCD at the molecular, structural, and functional levels.
Article
Cell Biology
Ian O. Shum, Sylvia Merkert, Svitlana Malysheva, Kirsten Jahn, Nico Lachmann, Murielle Verboom, Helge Frieling, Michael Hallensleben, Ulrich Martin
Summary: Abnormalities during trophoblast development can lead to pregnancy-related complications, but the underlying mechanisms are established during the first trimester. Human pluripotent stem cell (hPSC) technology provides a renewable source of cells for studying these diseases. By optimizing the treatment protocol, we were able to generate trophoblast cells enriched for HLA-G(pos) EVT-like cells, which will aid in understanding placenta-related disorders and investigation of immune tolerance towards the fetus.
Article
Biochemical Research Methods
Felix Manstein, Kevin Ullmann, Wiebke Triebert, Robert Zweigerdt
Summary: The protocol outlines controlled expansion of hPSCs in stirred tank bioreactors, achieving high cell densities while reducing culture medium consumption. It provides a detailed blueprint for systematic process development of hPSCs and their progenies.
