Article
Biochemistry & Molecular Biology
Akshay Narkar, James M. Willard, Ksenia Blinova
Summary: This review focuses on recent advances in chronic cardiotoxicity assessment using cardiomyocytes differentiated from human induced pluripotent stem cells. The review summarizes studies on chronic cardiotoxicity induced by various drugs, including anticancer agents, antibiotics, anti-HCV drugs, and antidiabetic drugs. The review also highlights the use of hiPSC-CMs in investigating the chronic effects of non-pharmaceutical cardiotoxicants and the development of biomarker assays. The comprehensive investigation of long-term repeated exposure-induced effects on cardiomyocytes can provide mechanistic insights and recapitulate drug and environmental cardiotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Xuehui Fan, Lukas Cyganek, Katja Nitschke, Stefanie Uhlig, Philipp Nuhn, Karen Bieback, Daniel Duerschmied, Ibrahim El-Battrawy, Xiaobo Zhou, Ibrahim Akin
Summary: This study compared the electrophysiological and functional properties of endothelial cells derived from human induced pluripotent stem cells with primary human cardiac microvascular endothelial cells. The results demonstrated that the two types of endothelial cells were similar in terms of ion channel function, membrane receptor signaling, and physiological cell functions, although some differences were observed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
John Lenon de Souza Santos, Cecilia de Almeida Araujo, Clarissa Araujo Gurgel Rocha, Zaquer Suzana Munhoz Costa-Ferro, Bruno Solano de Freitas Souza
Summary: Autism spectrum disorders (ASD) are complex neurodevelopmental disorders that affect communication and social interactions. The understanding of the cellular and molecular mechanisms underlying ASD is still limited. Recent advancements in cellular reprogramming technology have allowed the generation of patient-specific cell models for mechanistic studies. Brain organoids derived from these cells have provided significant advances in the reproducibility of early human brain development, contributing to the study of ASD.
Review
Medicine, Research & Experimental
Keyang Zhu, Xiaoming Bao, Yingchao Wang, Ting Lu, Ling Zhang
Summary: Cardiovascular disease (CVD) is the leading cause of death worldwide. Natural compounds extracted from medicinal plants, known for their diverse biological activities and low toxicity, are becoming more popular in the search for new drugs. However, the use of immortalized cell lines or animal models for preclinical evaluation of natural products has limitations in accurately recapitulating pathogenic phenotypes and translating to clinical relevance. The development of human induced pluripotent stem cell (hiPSC) technology combined with efficient cardiomyocyte differentiation methods provides an ideal platform for modeling human cardiomyopathies in vitro. Screening of drugs, especially natural products, based on these models has shown promise in recapitulating important physiological properties.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
C. Altrocchi, K. Van Ammel, M. Steemans, M. Kreir, F. Tekle, A. Teisman, D. J. Gallacher, H. R. Lu
Summary: This study developed an in vitro screening platform using human-induced pluripotent stem cell-derived cardiomyocytes to evaluate both acute and delayed electrophysiological and cytotoxic effects of reference compounds, which can contribute to the early assessment of drug-induced cardiotoxicity.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Engineering, Biomedical
Niall J. Treacy, Shane Clerkin, Jessica L. Davis, Ciaran Kennedy, Aline F. Miller, Alberto Saiani, Jacek K. Wychowaniec, Dermot F. Brougham, John Crean
Summary: Human induced pluripotent stem cell (hiPSC)-derived kidney organoids were matured within synthetic self-assembling peptide hydrogels (SAPHs) of variable stiffness. The organoids exhibited complex structures comparable to those differentiated within animal-derived matrix, Matrigel. Differentiation within a higher stiffness SAPH generated podocytes with more mature gene expression profiles. Maturing the organoids within a 3D microenvironment significantly reduced off-target cell types.
BIOACTIVE MATERIALS
(2023)
Article
Pharmacology & Pharmacy
William P. Bozza, Kazuyo Takeda, Wei-Lun Alterovitz, Chao-Kai Chou, Rong-Fong Shen, Baolin Zhang
Summary: Anthracyclines are effective chemotherapy drugs but their clinical use is limited by dose-dependent cardiotoxicity. This study used hiPSC-CMs and impedance measurement to monitor cardiomyocyte responses, comparing four structurally similar anthracycline drugs with different cardiotoxicity profiles. Results showed that differences in cardiotoxicity were linked to cardiomyocyte uptake and activation/inhibition of multiple cellular pathways.
Article
Cell & Tissue Engineering
Somayeh Pouyanfard, Nairika Meshgin, Luisjesus S. Cruz, Karin Diggle, Hamidreza Hashemi, Timothy Pham, Manuel Fierro, Pablo Tamayo, Andrea Fanjul, Tatiana Kisseleva, Dan S. Kaufman
Summary: The study shows that human iPSC-derived macrophages can effectively reduce gene expression and pathological markers of liver fibrosis, offering a promising cell therapy approach to ameliorate fibrosis.
Article
Multidisciplinary Sciences
Devansh Agarwal, Rian Kuhns, Christos N. N. Dimitriou, Emmalyn Barlow, Karl J. J. Wahlin, Ray A. A. Enke
Summary: Researchers utilized human pluripotent stem cell-derived 3D retinal organoids and Next Generation Sequencing to explore the gene regulation and cell fate determination in human retinal development, providing valuable reference for vision research.
Article
Cell Biology
Naresh Polisetti, Julian Rapp, Paula Liang, Viviane Dettmer-Monaco, Felicitas Bucher, Jan Pruszak, Ursula Schloetzer-Schrehardt, Toni Cathomen, Guenther Schlunck, Thomas Reinhard
Summary: hiPSC-LEPC and T-LEPC exhibit similar gene expression patterns, colony-forming ability, wound-healing capacity, and melanosome uptake, suggesting that hiPSC-LEPC could be a potential cell source for the treatment of LSCD.
Article
Cell Biology
Federica Fantuzzi, Sanna Toivonen, Andrea Alex Schiavo, Heeyoung Chae, Mohammad Tariq, Toshiaki Sawatani, Nathalie Pachera, Ying Cai, Chiara Vinci, Enrico Virgilio, Laurence Ladriere, Mara Suleiman, Piero Marchetti, Jean-Christophe Jonas, Patrick Gilon, Decio L. Eizirik, Mariana Igoillo-Esteve, Miriam Cnop
Summary: The study comprehensively characterized the functionality of iPSC-derived beta cells both in vitro and in vivo in humanized mice. Differentiation in microwells showed equal efficiency with rotating suspension, but with a higher success rate. In vivo transplanted beta cells demonstrated functional characteristics similar to human islets, highlighting the potential of generating islet-like organoids for diabetes research.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Neurosciences
Ari Ogaki, Yuji Ikegaya, Ryuta Koyama
Summary: Researchers have developed a method to efficiently transplant human induced pluripotent stem cell-derived microglia (hiPSC-MG) into mouse hippocampal slice cultures, achieving a high replacement rate. The transplanted microglia changed their morphology and phagocytosed cell debris when neuronal death was induced. This method provides a useful ex vivo tool for evaluating the properties of hiPSC-MG.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Gastroenterology & Hepatology
Tadahiro Shinozawa, Masaki Kimura, Yuqi Cai, Norikazu Saiki, Yosuke Yoneyama, Rie Ouchi, Hiroyuki Koike, Mari Maezawa, Ran-Ran Zhang, Andrew Dunn, Autumn Ferguson, Shodai Togo, Kyle Lewis, Wendy L. Thompson, Akihiro Asai, Takanori Takebe
Summary: This study established a screening model based on human liver organoids (HLO) for analyzing drug-induced liver injury (DILI) pathology, providing unique advantages at the organoid resolution. Through this model, a multi-readout organoid analysis was successfully developed to measure viability, cholestatic and/or mitochondrial toxicity, showing high predictive values for marketed drugs.
Review
Biochemistry & Molecular Biology
Mandeep Kumar, Nhung Thi Phuong Nguyen, Marco Milanese, Giambattista Bonanno
Summary: Astrocytes play a crucial role in neurodegenerative disorders, and the differentiation of human iPSCs into astrocytes has opened up new possibilities for disease modeling and drug screening. This advancement in research offers a promising avenue for exploring treatment strategies for neurodegenerative diseases.
Article
Cell & Tissue Engineering
Juliana Borsoi, Mariana Morato-Marques, Fabiano de Araujo Tofoli, Lucas Assis Pereira, Luis Ernesto Farinha-Arcieri, Raquel Delgado Sarafian, Ana Beatriz Alvarez Perez, Lygia Veiga Pereira
Summary: Marfan Syndrome is a pleiotropic and autosomal dominant condition caused by pathogenic variants in FBN1. The clinical variability among patients and the lack of clear genotype-phenotype correlations are notable. By generating and characterizing hiPSC lines from two unrelated MFS patients, researchers found that differentiated cells showed different patterns of fibrillin-1 expression, suggesting potential differences in molecular mechanisms between the two patients.
STEM CELL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Canelif Yilmaz, Thanasis Rogdakis, Alessia Latorrata, Evangelia Thanou, Eleftheria Karadima, Eleni Papadimitriou, Eleni Siapi, Ka Wan Li, Theodora Katsila, Theodora Calogeropoulou, Ioannis Charalampopoulos, Vasileia Ismini Alexaki
Summary: The newly synthesized small molecule ENT-A010 exhibited neuroprotective effects and modulated microglial function through the activation of the TRKA receptor signaling pathway, showing potential in the treatment of CNS disorders.
Article
Multidisciplinary Sciences
Sang S. Seo, Susana R. Louros, Natasha Anstey, Miguel A. Gonzalez-Lozano, Callista B. Harper, Nicholas C. Verity, Owen Dando, Sophie R. Thomson, Jennifer C. Darnell, Peter C. Kind, Ka Wan Li, Emily K. Osterweil
Summary: Dysregulated protein synthesis is a key contributing factor to the development of Fragile X syndrome. The authors of this study have identified a relationship between ribosome expression and the translation of long mRNAs, which is responsible for synaptic weakening in Fragile X syndrome.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Suzanne S. M. Miedema, Merel O. Mol, Frank T. W. Koopmans, David C. Hondius, Pim van Nierop, Kevin Menden, Christina F. de Veij Mestdagh, Jeroen van Rooij, Andrea B. Ganz, Iryna Paliukhovich, Shamiram Melhem, Ka Wan Li, Henne Holstege, Patrizia Rizzu, Ronald E. van Kesteren, John C. van Swieten, Peter Heutink, August B. Smit
Summary: By analyzing the proteomic signatures of frontal and temporal cortices from individuals with frontotemporal dementia due to specific genetic mutations, researchers identified distinct neurobiological mechanisms and cell types associated with different genetic subtypes, providing insight for the development of subtype-specific treatments.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Cell & Tissue Engineering
Johanna Heider, Denise Sperlich, Sabrina Vogel, Ricarda Breitmeyer, Hansjuergen Volkmer
Summary: DISC1 is a scaffold protein involved in key developmental processes, and genetic variants of the DISC1 gene have been linked to neuropsychiatric disorders. In this study, two isogenic iPSC lines carrying mutations in DISC1 exon 2 were generated using CRISPR/Cas9 gene editing, providing a means to study the implications of DISC1 mutations in the context of neuropsychiatric diseases in vitro.
STEM CELL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Jasmin Schaefer, Timm Danker, Karin Gebhardt, Udo Kraushaar
Summary: This article introduces a novel device that opens the membrane of cardiomyocytes using a nanosecond laser beam, enabling the conversion of extracellular field potentials to intracellular-like action potentials. This allows for a more accurate description of action potential shape and evaluation of cardiotoxic effects.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Biochemistry & Molecular Biology
Jessie W. Brunner, Hanna C. A. Lammertse, Annemiek A. van Berkel, Frank Koopmans, Ka Wan Li, August B. Smit, Ruud F. Toonen, Matthijs Verhage, Sophie van der Sluis
Summary: This study compares different designs and statistical analysis methods used in iPSC research, and finds that commonly used case-control designs are generally underpowered. The study suggests that multiple isogenic pair designs can increase power and require fewer lines. A free web tool is provided for exploring the power of different study designs using any (pilot) data.
MOLECULAR PSYCHIATRY
(2023)
Article
Neurosciences
Susana R. Louros, Sang S. Seo, Beatriz Maio, Cristina Martinez-Gonzalez, Miguel A. Gonzalez-Lozano, Melania Muscas, Nick C. Verity, Jimi C. Wills, Ka Wan Li, Matthew F. Nolan, Emily K. Osterweil
Summary: In fragile X syndrome, excessive neuronal protein synthesis is a core pathophysiology, but an overall increase in protein expression is not observed. Surprisingly, although protein degradation through the ubiquitin proteasome system (UPS) is significantly increased, this contributes to pathological changes. Normalizing proteasome activity corrects excessive protein synthesis and hyperactivation of neurons in response to auditory stimulation, reducing the incidence and severity of audiogenic seizures in the mouse model. Excessive activation of the UPS pathway in fragile X neurons can be targeted for therapeutic intervention.
Article
Cell Biology
Sophie J. F. van der Spek, Nikhil J. Pandya, Frank Koopmans, Iryna Paliukhovich, Roel C. van der Schors, Mylene Otten, August B. Smit, Ka Wan Li
Summary: AMPA glutamate receptor (AMPA-R) is the major excitatory ionotropic receptor at synapses in the brain. Different subunits and subtypes of AMPA receptors have different effects on synaptic plasticity and interact with various associated proteins. However, there is a lack of systematic analysis on the specific interactome of AMPA receptor subtypes.
Article
Clinical Neurology
Kimberly Wolzak, Lisa Vermunt, Marta del Campo, Marta Jorge-Oliva, Anna Maria van Ziel, Ka Wan Li, August B. Smit, Alice Chen-Ploktkin, David J. Irwin, Afina W. Lemstra, Yolande Pijnenburg, Wiesje van der Flier, Henrik Zetterberg, Johan Gobom, Kaj Blennow, Pieter Jelle Visser, Charlotte E. Teunissen, Betty M. Tijms, Wiep Scheper
Summary: This study has identified CSF biomarkers associated with early tau pathology-associated unfolded protein response (UPR) activation through biomarker discovery and validation. The levels of PDIA1 and PDIA3 correlate with total and phosphorylated tau levels in CSF, and PDIA1 levels are increased in AD patients compared to controls and patients with tau-unrelated dementia.
ALZHEIMERS & DEMENTIA
(2023)
Article
Biochemistry & Molecular Biology
Miao Chen, Frank Koopmans, Iryna Paliukhovich, Sophie J. F. van der Spek, Jian Dong, August B. Smit, Ka Wan Li
Summary: This study used an interaction proteomics workflow to reveal the existence of GABA(A) receptor subtypes containing both alpha 1 and alpha 6 subunits. Mass spectrometry analysis showed that these receptor subtypes exist in two main forms, with or without Neuroligin-2. Immunocytochemistry confirmed the presence of this synaptic GABA(A)R subtype at the synapse.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Evangelia Thanou, Frank Koopmans, Debora Pita-Illobre, Remco V. V. Klaassen, Berna Ozer, Ioannis Charalampopoulos, August B. B. Smit, Ka Wan Li
Summary: sTRAP is an effective sample preparation method for proteomics studies, using 5% SDS for protein solubilization and a borosilicate glass membrane filter to trap proteins. Compared to other methods, sTRAP outperforms in terms of protein and peptide identification numbers and coefficient of variation. sTRAP was successfully applied to analyze the hippocampal proteome in a mouse model of Alzheimer's disease, revealing changes in proteins related to the immune system and Amyloid aggregation.
Editorial Material
Neurosciences
Fereshteh S. S. Nugent, Ka Wan Li, Lu Chen
FRONTIERS IN SYNAPTIC NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Patricia Sinclair, Julia Hakeem, Dominik Loser, Kushan Dixit, Marcel Leist, Udo Kraushaar, Nadine Kabbani
Summary: Neonicotinoids are widely used pesticides and have been shown to be harmful to many organisms. They bind to human nicotinic acetylcholine receptors and cause cellular toxicity. In a recent study, the effects of imidacloprid and other neonics on cellular protein expression were examined, suggesting a role for protein synthesis and transcriptional regulation in neonic-mediated neurotoxicity.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2023)
Article
Biology
Ivona Mateska, Anke Witt, Eman Hagag, Anupam Sinha, Canelif Yilmaz, Evangelia Thanou, Na Sun, Ourania Kolliniati, Maria Patschin, Heba Abdelmegeed, Holger Henneicke, Waldemar Kanczkowski, Ben Wielockx, Christos Tsatsanis, Andreas Dahl, Axel Karl Walch, Ka Wan Li, Mirko Peitzsch, Triantafyllos Chavakis, Vasileia Ismini Alexaki
Summary: In this study, the researchers found that IL-1β reduced SDHB expression by upregulating DNMT1 and methylation of the SDHB promoter, disrupting the TCA cycle and leading to succinate accumulation and disturbed steroidogenesis. These findings provide a mechanistic explanation for adrenal dysfunction in severe inflammation and offer a potential target for therapeutic intervention.
Article
Cell Biology
Greta Pintacuda, Yu-Han H. Hsu, Kalliopi Tsafou, Ka Wan Li, Jacqueline M. Martin, Jackson Riseman, Julia C. Biagini, Joshua K. T. Ching, Daya Mena, Miguel A. Gonzalez-Lozano, Shawn B. Egri, Jake Jaffe, August B. Smit, Nadine Fornelos, Kevin C. Eggan, Kasper Lage
Summary: In this study, a protein-protein interaction network was constructed to reveal the expression patterns and interactions of genes associated with autism spectrum disorders (ASDs) in human excitatory neurons. The study identified important interactions among synaptic proteins, as well as a novel interaction influencing neuronal growth. Moreover, a complex that may regulate the transcriptional circuit of ASD-associated genes was also discovered.
