Article
Multidisciplinary Sciences
Ana Gonzalez-Ramos, Eliska Waloschkova, Apostolos Mikroulis, Zaal Kokaia, Johan Bengzon, Marco Ledri, My Andersson, Merab Kokaia
Summary: This study demonstrates the potential for regulating human neuronal network activity by transplanting light-sensitive GABAergic interneurons. It provides a new avenue for controlling neurological disorders through precise temporal modulation of network excitability.
SCIENTIFIC REPORTS
(2021)
Article
Cell & Tissue Engineering
Thomas Allison, Justin Langerman, Shan Sabri, Marcos Otero-Garcia, Andrew Lund, John Huang, Xiaofei Wei, Ranmal A. Samarasinghe, Damon Polioudakis, Istvan Mody, Inma Cobos, Bennett G. Novitch, Daniel H. Geschwind, Kathrin Plath, William E. Lowry
Summary: Studies have used single-nuclei and single-cell transcriptomics to model the development of inhibitory neurons in the human cortex and those derived from pluripotent stem cells (PSCs). The analyses show that PSC-derived inhibitory neurons capture early developmental stages in the brain, representing only a minority of potential subtypes with decreased expression of synapse-related genes. This highlights the potential to customize the generation method to drive the formation of specific subtypes.
Article
Biochemistry & Molecular Biology
Britt Mossink, Jon-Ruben Van Rhijn, Shan Wang, Katrin Linda, Maria R. Vitale, Johanna E. M. Zoller, Eline J. H. van Hugte, Jitske Bak, Anouk H. A. Verboven, Martijn Selten, Moritz Negwer, Brooke L. Latour, Ilse van der Werf, Jason M. Keller, Teun M. Klein Gunnewiek, Chantal Schoenmaker, Astrid Oudakker, Alessia Anania, Sophie Jansen, Klaus-Peter Lesch, Monica Frega, Hans van Bokhoven, Dirk Schubert, Nael Nadif Kasri
Summary: This study revealed the regulatory role of CDH13 in inhibitory synapse function by establishing a human neuronal model. By culturing iGABAs in vitro, we found that CDH13 deficiency increases inhibition, thereby reducing the excitatory/inhibitory balance. Through these findings, we identified a potential mechanism by which CDH13 may contribute to the pathophysiology of brain disorders.
MOLECULAR PSYCHIATRY
(2022)
Article
Multidisciplinary Sciences
Ana Gonzalez-Ramos, Kerstin Laurin, Fredrik Berglind, Marco Ledri, Merab Kokaia, My Andersson
Summary: Reduced number or dysfunction of inhibitory interneurons is a common contributor to neurodevelopmental disorders. This study focuses on using cell therapy to replace or mitigate the effects of altered neuronal circuits. Human stem cell-derived GABAergic interneuron-like cells (hdINs) are generated using a transgenic approach and transplanted into the hippocampus of neonatal mice. The transplanted neurons survive and integrate into both the ipsi- and contralateral hippocampus, providing insights into their cellular identity, integration, functionality, and therapeutic potential in healthy and diseased brains.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Biochemistry & Molecular Biology
Charles A. Herring, Rebecca K. Simmons, Saskia Freytag, Daniel Poppe, Joel J. D. Moffet, Jahnvi Pflueger, Sam Buckberry, Dulce B. Vargas-Landin, Olivier Clement, Enrique Goni Echeverria, Gavin J. Sutton, Alba Alvarez-Franco, Rui Hou, Christian Pflueger, Kerrie McDonald, Jose M. Polo, Alistair R. R. Forrest, Anna K. Nowak, Irina Voineagu, Luciano Martelotto, Ryan Lister
Summary: This study reveals the dynamic trajectories and regulatory mechanisms of different cell types during human prefrontal cortex development through single-cell resolution analysis of gene expression and chromatin accessibility. The findings provide important clues for understanding neurodevelopment and neurological disorders.
Article
Biochemistry & Molecular Biology
Maria G. Otero, Shaughn Bell, Alexander H. Laperle, George Lawless, Zachary Myers, Marian A. Castro, Jaquelyn M. Villalba, Clive N. Svendsen
Summary: Conventional tissue culture platforms limit the study of cell biology due to lack of maturity, while organ-chip microfluidic systems provide a more physiological environment for cell growth. In this study, organ-chip cultures showed a higher proportion and homogeneity of mature dopamine neurons compared to multi-well cultures. These organ-chips are ideal for studying the biology of mature dopamine neurons in health and neurological disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell & Tissue Engineering
Suguru Yamasaki, Sunao Sugita, Matsuri Horiuchi, Tomohiro Masuda, Shota Fujii, Kenichi Makabe, Akihiro Kawasaki, Takuya Hayashi, Atsushi Kuwahara, Akiyoshi Kishino, Toru Kimura, Masayo Takahashi, Michiko Mandai
Summary: Research has shown that hESC- and iPSC-derived retinas express low levels of HLA-I and minimal HLA-II in vitro, possess the ability to suppress immune activation of lymphocytes in co-culture, and partially suppress activated immune cells via the transforming growth factor β signaling pathway. These findings support the potential use of allogeneic hESC- and iPSC-derived retinal transplantation in future clinical applications.
Article
Biochemistry & Molecular Biology
Juan Yu, Nianye Yu, Yao Tian, Yifan Fang, Bin An, Guihai Feng, Jun Wu, Liu Wang, Jie Hao, Liqiang Wang, Qi Zhou, Wei Li, Yukai Wang, Baoyang Hu
Summary: Our study presents an improved protocol for differentiating clinical-grade hESCs into iCECs using xeno-free medium and cryopreservation. The generated iCECs express typical CECs markers and exhibit transendothelial potential properties. After rigorous quality control, the cells meeting release criteria were available for in vivo studies. Grafts of iCECs did not show overgrowth or tumorigenicity in immunodeficient mice and successfully ameliorated edema and corneal opacity in rabbit models.
CELL AND BIOSCIENCE
(2023)
Article
Cell & Tissue Engineering
Ke Ning, Ziming Luo, Tia J. J. Kowal, Matthew Tran, Rishab Majumder, Trent M. M. Jarin, Albert Y. Y. Wu, Jeffrey L. L. Goldberg, Yang Sun
Summary: This study aims to characterize the distribution of primary cilia in human embryonic stem cell-derived retinal organoids. Immunostaining of the organoids at different developmental stages revealed the presence of ciliated cells in the inner aspects of the organoids, including photoreceptor cells, astrocytes, and rod-bipolar cells. However, ciliation gradually decreased in retinal ganglion cells with organoid maturation.
STEM CELLS INTERNATIONAL
(2023)
Article
Nanoscience & Nanotechnology
Syed Baseeruddin Alvi, Divya Sridharan, Shridhar K. Sanghvi, Muhamad Mergaye, Uzair Ahmed, Sarah K. Mikula, Harpreet Singh, Mahmood Khan
Summary: This study demonstrates the potential of polydopamine nanoparticles (PDA-NPs) as a bioactive agent to enhance contractility and beat propagation of cardiomyocytes. PDA-NPs improve mitochondrial bioenergetics and have cardiotonic effects on the heart. In addition, they can modulate the genetic expression of cardiomyocytes.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Biochemistry & Molecular Biology
Debkanya Datta, Sivan Subburaju, Sarah Kaye, Jugajyoti Baruah, Yong Kee Choi, Yeqi Nian, Jahan S. Khalili, Sangmi Chung, Abdallah Elkhal, Anju Vasudevan
Summary: The study demonstrates that transplantation of human stem cell-derived interneurons is a promising therapy for severe neuropsychiatric disorders, but the slow migration rate poses a challenge for clinical application. Co-culture of human periventricular endothelial cells with interneurons significantly accelerates migration, leading to faster distribution and rescue of abnormal behaviors in a pre-clinical model of psychiatric disorder within one month. This strategy opens up new possibilities for treating neuropsychiatric disorders.
MOLECULAR PSYCHIATRY
(2021)
Article
Cell Biology
Jinghui Lei, Xiaoyu Jiang, Daoyuan Huang, Ying Jing, Shanshan Yang, Lingling Geng, Yupeng Yan, Fangshuo Zheng, Fang Cheng, Weiqi Zhang, Juan Carlos Izpisua Belmonte, Guang-Hui Liu, Si Wang, Jing Qu
Summary: Using CRISPR/Cas9 gene editing, researchers investigated the response mechanism of human vascular cells to HIF-1α under hypoxic conditions. They found that HIF-1α plays an important role in promoting ischemic vascular regeneration and that MSCs are particularly susceptible to HIF-1α deficiency. Transcriptional inactivation of ANKZF1, an effector of HIF-1α, was found to impair pro-angiogenic processes.
Article
Engineering, Biomedical
Roma Borkar, Xiaoyan Wang, Dejin Zheng, Zhengqiang Miao, Zhenwu Zhang, Enqin Li, Yaojiong Wu, Ren-He Xu
Summary: Research has shown that differentiation of embryonic stem cells into mesenchymal stem cells and transplantation with fat tissue into nude mice can enhance fat engraftment through tissue reconstitution, angiogenesis, increased adipocyte survival, and reduced fibrosis. This effect is mediated by stimulated CCL2 signaling and mobilized macrophages in promoting the engraftment of fat tissue.
Article
Nanoscience & Nanotechnology
Dovile Strimaityte, Chengyi Tu, Apuleyo Yanez, Ilanit Itzhaki, Haodi Wu, Joseph C. Wu, Huaxiao Yang
Summary: In this study, engineered cardiac microfibers were created using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to enhance their maturity and functionality. The results showed improved sarcomere organization, contractility, calcium transient, and junction formation in the hiPSC-CMs in the microfibers compared to other patterns. These findings highlight the potential of hiPSC-CM models for disease modeling and regenerative medicine.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Cell Biology
Liang Ye, Xinyuan Zhang, Qin Zhou, Bin Tan, Hao Xu, Qin Yi, Liang Yan, Min Xie, Yin Zhang, Jie Tian, Jing Zhu
Summary: Activation of AMPK improves the maturation of hiPSC-CMs by increasing the expression of CM-specific markers, improving myocardial structure, enhancing mitochondrial function, and promoting mitochondrial fusion.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
