Review
Cell Biology
Wajima Safi, Andres Marco, Daniel Moya, Patricia Prado, Elena Garreta, Nuria Montserrat
Summary: The differentiation of human pluripotent stem cells towards kidney organoids has advanced regenerative medicine significantly. Understanding the developmental pathways of nephrogenesis has enabled the in vitro recapitulation of kidney development. Genome editing approaches, such as CRISPR/Cas9 technology, have provided insights into specific gene functions during renal differentiation from hPSCs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Anika Schumacher, Nadia Roumans, Timo Rademakers, Virginie Joris, Maria Jose Eischen-Loges, Martijn van Griensven, Vanessa L. S. LaPointe
Summary: Studying the modulation of oxygen availability in culture, researchers found that culturing kidney organoids in hypoxia can lead to improved vascularization. The endothelial network in kidney organoids cultured in hypoxia showed enhanced sprouting and interconnectivity.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Review
Cell Biology
Brooke E. Chambers, Nicole E. Weaver, Rebecca A. Wingert
Summary: Kidney organoids are three-dimensional cellular aggregates derived from stem cells that mimic normal renal development and can be used to study kidney diseases and drug screening. Recent advances in organoid technologies have improved their complexity and reproducibility, making them more suitable for high-throughput experimentation. However, challenges still exist in utilizing kidney organoids for renal replacement therapies. This review provides an overview of the kidney organoid field and highlights recent research in embryonic development, disease modeling, and personalized drug screening.
Article
Biochemistry & Molecular Biology
Yapei Yuan, Huan Chen, Sihua Ou, Baomei Cai, Ruifang Zhang, Yue Qin, Mengjie Pan, Shangtao Cao, Duanqing Pei, Fan Fan Hou
Summary: This study successfully generated mitochondria-rich kidney organoids via partial reprogramming of human urine cells, which recapitulated the structural and functional characteristics of the kidneys, providing a promising model to study mitochondria-related kidney physiology and disease in a personalized manner.
CELL AND BIOSCIENCE
(2022)
Article
Cell Biology
Gurmannat Kalra, Daniell Lenz, Dunia Abdul-Aziz, Craig Hanna, Mahashweta Basu, Brian R. Herb, Carlo Colantuoni, Beatrice Milon, Madhurima Saxena, Amol C. Shetty, Ronna Hertzano, Ramesh A. Shivdasani, Seth A. Ament, Albert S. B. Edge
Summary: In this study, we examined the changes in chromatin accessibility and transcriptional programs during the differentiation of cochlear hair cells from postmitotic supporting cells using organoids. We identified Lgr5+ cells as the progenitors for hair cells and revealed the gene regulatory networks involved in their development. The analysis also predicted the involvement of additional regulatory factors in hair cell regeneration. This study provides important insights into the signals for hair cell regeneration from mammalian supporting cells.
Article
Chemistry, Multidisciplinary
Zhong Zhang, Shan Gao, Yang-Nan Hu, Xin Chen, Cheng Cheng, Xiao-Long Fu, Sha-Sha Zhang, Xin-Lin Wang, Yu-Wei Che, Chen Zhang, Ren-Jie Chai
Summary: This study incorporates MXene nanomaterial into Matrigel to regulate its properties, promoting the formation and maturation of hair cells in cochlear organoids. MXene-Matrigel enhances hair cell differentiation by potentiating the mTOR signaling pathway and promotes synapse formation. The research overcomes limitations of the Matrigel-dependent culture system and is significant for organoid development and hearing loss therapy research.
Article
Biochemistry & Molecular Biology
Sabrina Leverrier-Penna, Alain Michel, Laetitia L. Lecante, Nathalie Costet, Antonio Suglia, Christele Desdoits-Lethimonier, Hugoline Boulay, Roselyne Viel, Jonathan M. Chemouny, Emmanuelle Becker, Vincent Lavoue, Antoine D. Rolland, Nathalie Dejucq-Rainsford, Cecile Vigneau, Severine Mazaud-Guittot
Summary: This study investigated the effects of analgesics on human fetal kidneys during early pregnancy, revealing a spectrum of abnormalities induced by these drugs, ranging from cell death to a decline in differentiating glomeruli density. Caution is warranted for the use of these medications during the first trimester of pregnancy.
Review
Neurosciences
Meiyan Wang, Fred H. Gage, Simon T. Schafer
Summary: Human brain organoids generated from pluripotent stem cells recapitulate early developing human brain features but lack functional vasculature and non-neuronal cells. Recent progress in intracerebral transplantation approaches has demonstrated successful vascularization and neurodifferentiation of brain organoids. Ethical considerations in the field of brain organoid transplantation are also discussed.
BIOLOGICAL PSYCHIATRY
(2023)
Review
Biochemistry & Molecular Biology
Liang-Ti Huang, Chung-Ming Chen
Summary: Preterm birth and hyperoxia exposure disrupt the development and function of the kidneys, leading to the pathogenesis of chronic kidney disease. Hyperoxia-induced kidney injuries are mediated by various molecular factors, including hypoxia-inducible factor-1 alpha, interleukin-6/Smad2/transforming growth factor-beta, and Wnt/beta-catenin signaling pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Jessica M. Vanslambrouck, Ker Sin Tan, Sophia Mah, Melissa H. Little
Summary: This article describes an improved method for generating kidney organoids with better proximal tubule maturity from human pluripotent stem cells. The enhanced organoids show increased expression of critical transporters and improved functionality, as assessed by substrate uptake and transport.
Article
Biochemistry & Molecular Biology
Fenglin Wang, Jenny Ngo, Yuwen Li, Hongbing Liu, Chao-Hui Chen, Zubaida Saifudeen, Maria Luisa S. Sequeira-Lopez, Samir S. El-Dahr
Summary: Dot1, an epigenetic regulator, plays crucial roles in organismal development and homoeostasis by regulating telomeric silencing, genomic integrity, and homoeotic gene expression. Studies in fruit flies and mice have shown that Dot1 functions differently in various cell lineages, particularly in the development of the kidney. The link between H3K79me and renal developmental pathways highlights the importance of chromatin-based mechanisms in organogenesis.
Article
Biochemical Research Methods
Min Shi, Ping Fu, Joseph V. Bonventre, Kyle W. McCracken
Summary: Developing in vitro models of human kidney tissue using human pluripotent stem cells (hPSCs) is challenging but essential for regenerative nephrology research. This article describes a step-by-step protocol for differentiating hPSCs into three-dimensional ureteric bud (UB) organoids, which exhibit complex morphological development and can differentiate into functional collecting duct tissues. This approach provides a robust and reproducible method for generating UB tissues that can be used to study kidney development, model disease processes, and aid in the engineering of functional kidney tissue.
Article
Multidisciplinary Sciences
Tomoko Ohmori, Shankhajit De, Shunsuke Tanigawa, Koichiro Miike, Mazharul Islam, Minami Soga, Takumi Era, Shinichi Shiona, Koichi Nakanishi, Hitoshi Nakazato, Ryuichi Nishinakamura
Summary: In this study, iPSCs were generated from two additional patients with different NPHS1 mutations, and podocyte abnormalities in kidney organoids derived from these cells were examined. One patient had truncating mutations resulting in undetectable NEPHRIN in the organoids. The other patient had a missense mutation (R460Q) causing mutant NEPHRIN to fail to accumulate on the podocyte surface to form SD precursors. This suggests that NEPHRIN localization is cell context-dependent.
SCIENTIFIC REPORTS
(2021)
Article
Cell & Tissue Engineering
Stephan A. Ramos, Lucas H. Armitage, John J. Morton, Nathaniel Alzofon, Diana Handler, Geoffrey Kelly, Dirk Homann, Antonio Jimeno, Holger A. Russ
Summary: The thymus is crucial for a functional immune system, but it involutes with age, leading to reduced T cell output. Researchers have developed stem cell-derived thymic organoids that can generate functional thymic epithelial cells (TECs) in vitro. These organoids support T cell development and express markers of negative selection, making them useful for studying thymus function and T cell development.
Article
Cell & Tissue Engineering
Lin Cheng, Matthew R. Cring, David A. Wadkins, Markus H. Kuehn
Summary: This study used CRISPR/Cas9 editing to disrupt the GJA1 gene in human-induced pluripotent stem cells, resulting in developmental abnormalities in retinal organoids. Lack of CX43 protein led to decreased retinal cell types and disrupted retinal organoid development.
Article
Urology & Nephrology
Jan Wysocki, Minghao Ye, Luise Hassler, Ashwani Kumar Gupta, Yuguo Wang, Vlad Nicoleascu, Glenn Randall, Jason A. Wertheim, Daniel Batlle
Summary: A novel ACE2 variant has been developed that can neutralize SARS-CoV-2 infectivity in human kidney organoids, with prolonged duration of action and potential for improved efficacy.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Oncology
Kyle H. Bond, Jennifer L. Fetting, Christine W. Lary, Ivette F. Emery, Leif Oxburgh
Summary: The study reveals that FOXD1 regulates the cell cycle in ccRCC cells by controlling histone H3 phosphorylation and governs tumor formation and growth. Transcriptome analysis supports this role for FOXD1 in ccRCC patient tumors and explains the inverse correlation between FOXD1 expression and patient survival.
Article
Developmental Biology
Anne R. Ryan, Alicia R. England, Christopher P. Chaney, Mitzy A. Cowdin, Max Hiltabidle, Edward Daniel, Ashwani Kumar Gupta, Leif Oxburgh, Thomas J. Carroll, Ondine Cleaver
Summary: Kidney organoids offer a promising model system to study vascular-nephron interactions, but face unique challenges in establishing and maintaining a vascular network when grown ex vivo.
DEVELOPMENTAL BIOLOGY
(2021)
Article
Urology & Nephrology
Shimrit Avraham, Ben Korin, Jun-Jae Chung, Leif Oxburgh, Andrey S. Shaw
Summary: Mesangial cells are essential stromal cells in maintaining kidney glomerular homeostasis and responding to injury. Other mesenchymal stromal cells play roles in tissue architecture, developmental processes, vascularization, and cell fate determination. These stromal cells can also regulate a variety of processes through crosstalk with neighboring cells and matrix remodeling, potentially impacting immunity, inflammation, regeneration, and fibrosis. Insights into the molecular phenotype of kidney mesangial cells provide a better understanding of kidney disease pathogenesis and the development of new therapies for chronic kidney disease.
NATURE REVIEWS NEPHROLOGY
(2021)
Article
Developmental Biology
Sarah S. McCarthy, Michele Karolak, Leif Oxburgh
Summary: Expansion of interstitial cells in adult kidney is a hallmark of chronic disease, while their proliferation during fetal development is necessary for organ formation. Inactivation of TGF beta/Smad response in mouse interstitial cell lineage leads to overproliferation of interstitial cells regionally in the kidney medulla. Smad4 loss primarily reduces TGF beta signaling in the interstitium, while increasing Wnt/beta-catenin signaling.
Editorial Material
Urology & Nephrology
Leif Oxburgh
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Oncology
Kyle H. Bond, Takuto Chiba, Kieran P. H. Wynne, Calvin P. H. Vary, Sunder Sims-Lucas, Jeannine M. Coburn, Leif Oxburgh
Summary: The study demonstrates the dependence of clear cell renal cell carcinoma (ccRCC) tumor cells and cancer-associated fibroblasts (CAFs) on the extracellular protein composition, providing a technology to investigate interactions between these cells.
Article
Oncology
Kyle H. Bond, Sunder Sims-Lucas, Leif Oxburgh
Summary: This study identifies important pathways regulated by FOXD1, which have therapeutic potential for inhibiting the growth of clear cell renal cell carcinoma (ccRCC) cells. Inhibiting these pathways using compounds can effectively suppress tumor growth. The use of a 3D tumor model further validates the inhibitory effects of the compounds. This research has significant implications for therapeutic targets to control ccRCC tumor growth and provides a platform for individualized testing of compounds that inhibit tumor growth.
Article
Cell & Tissue Engineering
Katherine E. Hekman, Kyle M. Koss, David Z. Ivancic, Congcong He, Jason A. Wertheim
Summary: This study addresses the limitations of using patient-specific induced pluripotent stem cell-derived endothelial cells in clinical and research applications. By increasing autophagy activity, the stability and longevity of these cells can be improved. This has significant implications for organ engineering and personalized therapies for vascular disease.
STEM CELLS TRANSLATIONAL MEDICINE
(2022)
Review
Oncology
Leif Oxburgh
Summary: The extracellular matrix (ECM) plays a critical role in controlling the growth, blood vessel investment, and invasion of tumors. In clear cell renal cell carcinoma (ccRCC), the inactivation of VHL gene, a common genetic mutation, leads to modifications in the ECM, promoting tumor cell growth and blood vessel invasion. Understanding the composition and functions of ccRCC ECM is essential for developing ECM-modifying drugs for this type of cancer.
Meeting Abstract
Surgery
A. Kumar Gupta, E. Minocha, J. A. Wertheim, L. Gallon
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Meeting Abstract
Gastroenterology & Hepatology
Andrew Benintende, Mark Antkowiak, Jason A. Wertheim, Richard M. Green
Article
Cell Biology
Prativa Das, Michael D. DiVito, Jason A. Wertheim, Lay Poh Tan
Summary: The study showed that the C:F_3:1 scaffold could maintain the translational and transcriptional properties of human liver cells and exhibited higher albumin secretion even under alcohol treatment. Additionally, LX-2 cells on the C:F_3:1 scaffold displayed a more quiescent phenotype compared to the gold standard sandwich culture when exposed to alcohol.
INTEGRATIVE BIOLOGY
(2021)