Review
Engineering, Multidisciplinary
Ikki Horiguchi, Masahiro Kino-oka
Summary: Induced pluripotent stem cells (iPSCs) are considered promising cell sources for regenerative medicine and drug screening, but effective mass production systems are still lacking. Various factors such as nutrient supply, waste removal, and oxygen availability need to be controlled for stable iPSC production. Multidisciplinary investigations are essential for understanding the factors influencing cell growth and quality in order to achieve an optimal and stable iPSC mass production system.
Correction
Cell & Tissue Engineering
Ran Zheng, Ting Geng, Dan-Ya Wu, Tianzhe Zhang, Hai-Nan He, Hai-Ning Du, Donghui Zhang, Yi-Liang Miao, Wei Jiang
Summary: A new method has been developed to convert human embryonic stem cells and induced pluripotent stem cells into EPSCs using chemicals, demonstrating extended pluripotency in terms of molecular features, chimeric ability, and transcriptome. Certain chemicals targeting glycolysis and histone methyltransferase have been identified to facilitate the conversion and maintenance of feeder-free EPSCs, providing insights for further research and applications in the field of pluripotency.
Article
Engineering, Chemical
Laura Herbst, Ferdinand Groten, Mary Murphy, Georgina Shaw, Bastian Niessing, Robert H. Schmitt
Summary: This study presents an adaptable and modular automation concept for handling the expansion, differentiation, and purification of iPSCs through integration of existing automation technologies, in order to meet the requirements of clinical production.
Article
Engineering, Biomedical
Bin Jiang, Weijie Li, Samantha Stewart, Wenquan Ou, Baolin Liu, Pierre Comizzoli, Xiaoming He
Summary: The study found that natural sand can seed ice above -10 degrees C, allowing hiPSCs to be cryopreserved without serum and with reduced cryoprotectants, leading to high cell survival. The cryopreserved hiPSCs also retained high pluripotency and functions.
BIOACTIVE MATERIALS
(2021)
Article
Cell & Tissue Engineering
Ran Zheng, Ting Geng, Dan-Ya Wu, Tianzhe Zhang, Hai-Nan He, Hai-Ning Du, Donghui Zhang, Yi-Liang Miao, Wei Jiang
Summary: This study introduces a feeder-free method to convert human embryonic stem cells and induced pluripotent stem cells into EPSCs, demonstrating their extended pluripotency in terms of molecular features, chimeric ability, and transcriptome. Additionally, it identifies chemicals targeting glycolysis and histone methyltransferase to facilitate the conversion and maintenance of feeder-free EPSCs.
Article
Engineering, Biomedical
Debbie L. L. Ho, Stacey Lee, Jianyi Du, Jonathan D. D. Weiss, Tony Tam, Soham Sinha, Danielle Klinger, Sean Devine, Art Hamfeldt, Hope T. T. Leng, Jessica E. E. Herrmann, Mengdi He, Lee G. G. Fradkin, Tze Kai Tan, David Standish, Peter Tomasello, Donald Traul, Noushin Dianat, Rukmini Ladi, Quentin Vicard, Kishore Katikireddy, Mark A. A. Skylar-Scott
Summary: By combining sustainable culture of billions of human cells and bioprinting of cellular bioinks, this study demonstrates an approach to tissue engineering at organ-scale. The research optimized the suspension culture and successfully scaled it up, while maintaining pluripotency, and then used 3D bioprinting to differentiate the pluripotent aggregates into different cell lines.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Computer Science, Interdisciplinary Applications
Benedikt X. Scholz, Yusuke Hayashi, Isuru A. Udugama, Masahiro Kino-oka, Hirokazu Sugiyama
Summary: This study presents a multilayered model-based approach for scaling up slow and forced convection-based freezing of human induced pluripotent stem cells. The approach combines a hybrid single-cell freezing model with a computational fluid dynamics model, and takes into account the spatial and timedependent temperature profiles within the freezer unit in calculating the cell survival rate.
COMPUTERS & CHEMICAL ENGINEERING
(2022)
Review
Biochemistry & Molecular Biology
Giuliana Minani Bertolino, Marie Maumus, Christian Jorgensen, Daniele Noel
Summary: Extracellular vesicles (EVs) isolated from induced pluripotent stem cells (iMSCs) show promise in regenerative medicine for the treatment of various diseases. However, the heterogeneity between MSC donors may lead to batch-to-batch variability in the use of EVs as cell-free therapeutic agents.
Article
Engineering, Biomedical
Jiesi Luo, Yuyao Lin, Xiangyu Shi, Guangxin Li, Mehmet H. Kural, Christopher W. Anderson, Matthew W. Ellis, Muhammad Riaz, George Tellides, Laura E. Niklason, Yibing Qyang
Summary: Research successfully derived functional xenogeneic-free hiPSC-VSMCs by replacing animal-derived reagents with functional counterparts of human origin, and developed tissue rings with comparable mechanical strength. Engineered vascular tissues were generated by seeding XF-hiPSC-VSMCs onto biodegradable PGA scaffolds, suitable for implantation into an immunodeficient mice model.
ACTA BIOMATERIALIA
(2021)
Article
Cell & Tissue Engineering
Kyle B. Lupo, Jung-Il Moon, Andrea M. Chambers, Sandro Matosevic
Summary: This study explored the differentiation of NK cells from iPSCs under defined conditions and evaluated their immunotherapeutic potential against solid tumors. The results showed that iPSC-NK cells exhibited effector functions against tumor cells, suggesting their promising application in clinical adoptive transfer settings for immunotherapy of solid tumors.
Article
Engineering, Biomedical
Jiesi Luo, Xiangyu Shi, Yuyao Lin, Yifan Yuan, Mehmet H. Kural, Juan Wang, Matthew W. Ellis, Christopher W. Anderson, Shang-Min Zhang, Muhammad Riaz, Laura E. Niklason, Yibing Qyang
Summary: The study successfully developed xenogeneic-free conditions for deriving functional endothelial cells from human induced pluripotent stem cells (XF-hiPSC-ECs), which exhibited similar marker expression and function to human primary ECs. Moreover, the XF-hiPSC-ECs responded to shear stress with typical cell alignment and gene expression, and were successfully used to endothelialize decellularized human vessels in a dynamic bioreactor system, advancing the potential clinical application of tissue engineered vascular grafts.
ACTA BIOMATERIALIA
(2021)
Review
Cell Biology
Giuseppe Novelli, Paola Spitalieri, Michela Murdocca, Eleonora Centanini, Federica Sangiuolo
Summary: In recent years, hiPSC-derived organoids have been extensively studied and used as in vitro models, especially for difficult-to-obtain organs and tissues. Various diseases can be accurately modeled and studied using these organoids. Patient-derived organoids (PDOs) can be used to predict individual drug responses for personalized medicine. Additionally, tissue engineering and 3D printing techniques could be used to replace or regenerate damaged tissue in the future.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Ying Zhang, Jun Wei, Jiani Cao, Kehua Zhang, Yaojin Peng, Hongkui Deng, Jiuhong Kang, Guangjin Pan, Yong Zhang, Boqiang Fu, Shijun Hu, Jie Na, Yan Liu, Lei Wang, Lingmin Liang, Huanxin Zhu, Yu Zhang, Zi-Bing Jin, Jie Hao, Aijin Ma, Tongbiao Zhao, Junying Yu
Summary: "Requirements for Human-Induced Pluripotent Stem Cells" is the first set of guidelines in China on human-induced pluripotent stem cells. It provides detailed technical requirements and aims to promote international standardization.
CELL PROLIFERATION
(2022)
Article
Engineering, Biomedical
Hong Cao, Qian Zhou, Chungeng Liu, Yecen Zhang, Minghui Xie, Weihua Qiao, Nianguo Dong
Summary: This study investigates the effect of substrate stiffness on the differentiation of human-induced pluripotent stem cells (h-iPSCs) into valve endothelial-like cells (h-iVECs). The results show that moderate substrate stiffness can enhance the differentiation efficiency of h-iVECs and is regulated by the WNT/Calcineurin signaling pathway. This study emphasizes the importance of using substrate stiffness to achieve a more specific and mature differentiation of h-iVECs.
ACTA BIOMATERIALIA
(2022)
Article
Medicine, Research & Experimental
Ruslan Rust, Rebecca Z. Weber, Melanie Generali, Debora Kehl, Chantal Bodenmann, Daniela Uhr, Debora Wanner, Kathrin J. Zuercher, Hirohide Saito, Simon P. Hoerstrup, Roger M. Nitsch, Christian Tackenberg
Summary: In this study, transgene- and xeno-free neural progenitor cells (NPCs) were generated for potential clinical applications. These cells had stable gene expression, could be expanded, and spontaneously differentiated into mature neurons. This research presents a valuable tool for safe and effective cell therapies for brain injuries.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Casey A. Rimland, Samantha G. Tilson, Carola M. Morell, Rute A. Tomaz, Wei-Yu Lu, Simone E. Adams, Nikitas Georgakopoulos, Francisco Otaizo-Carrasquero, Timothy G. Myers, John R. Ferdinand, Richard L. Gieseck, Fotios Sampaziotis, Olivia C. Tysoe, Alexander Ross, Judith M. Kraiczy, Brandon Wesley, Daniele Muraro, Matthias Zilbauer, Gabriel C. Oniscu, Nicholas R. F. Hannan, Stuart J. Forbes, Kourosh Saeb-Parsy, Thomas A. Wynn, Ludovic Vallier
Summary: Researchers successfully established organoids derived from human gallbladder, common bile duct, pancreatic duct, and IHBDs, expressing stem/progenitor and ductal markers, but conserving only limited regional-specific markers, with differences in response and expression of cell markers between IHBD and EHBD organoids.
Article
Multidisciplinary Sciences
Fotios Sampaziotis, Daniele Muraro, Olivia C. Tysoe, Stephen Sawiak, Timothy E. Beach, Edmund M. Godfrey, Sara S. Upponi, Teresa Brevini, Brandon T. Wesley, Jose Garcia-Bernardo, Krishnaa Mahbubani, Giovanni Canu, Richard Gieseck, Natalie L. Berntsen, Victoria L. Mulcahy, Keziah Crick, Corrina Fear, Sharayne Robinson, Lisa Swift, Laure Gambardella, Johannes Bargehr, Daniel Ortmann, Stephanie E. Brown, Anna Osnato, Michael P. Murphy, Gareth Corbett, William T. H. Gelson, George F. Mells, Peter Humphreys, Susan E. Davies, Irum Amin, Paul Gibbs, Sanjay Sinha, Sarah A. Teichmann, Andrew J. Butler, Teik Choon See, Espen Melum, Christopher J. E. Watson, Kourosh Saeb-Parsy, Ludovic Vallier
Summary: The study demonstrates the potential of cholangiocyte organoids to repair human biliary epithelium, despite the loss of transcriptional diversity during organoid culture, they remain plastic and have regenerative capabilities.
Article
Cell & Tissue Engineering
Stefania Carobbio, Anne-Claire Guenantin, Myriam Bahri, Sonia Rodriguez-Fdez, Floris Honig, Ioannis Kamzolas, Isabella Samuelson, Kathleen Long, Sherine Awad, Dunja Lukovic, Slaven Erceg, Andrew Bassett, Sasha Mendjan, Ludovic Vallier, Barry S. Rosen, Davide Chiarugi, Antonio Vidal-Puig
Summary: The research team has developed a new chemically defined protocol for differentiating human pluripotent stem cells into brown adipocytes, overcoming limitations in BAT research. The obtained brown adipocytes express markers and respond to stimuli.
Article
Gastroenterology & Hepatology
Samantha G. Tilson, Carola M. Morell, An-Sofie Lenaerts, Seung Bum Park, Zongyi Hu, Benjamin Jenkins, Albert Koulman, T. Jake Liang, Ludovic Vallier
Summary: The study used hiPSCs and CRISPR/CAS9 technology to develop an in vitro model to investigate the impact of the PNPLA3 gene and its variants on NAFLD development, revealing that the I148M variant induces loss of function, making patients more susceptible to fatty liver and liver toxins.
Article
Biology
Anna Osnato, Stephanie Brown, Christel Krueger, Simon Andrews, Amanda J. Collier, Shota Nakanoh, Mariana Quiroga Londono, Brandon T. Wesley, Daniele Muraro, A. Sophie Brumm, Kathy K. Niakan, Ludovic Vallier, Daniel Ortmann, Peter J. Rugg-Gunn
Summary: TGF beta signaling is essential for maintaining naive human pluripotent stem cells, with downstream effector proteins SMAD2/3 binding to common sites in both naive and primed cells. Inhibition of TGF beta signaling leads to downregulation of target genes and differentiation of pluripotent cells, with different transcriptional trajectories observed between naive and primed cells. These findings indicate a continuum of TGF beta pathway function in human pluripotency.
Article
Biology
Kirsty M. L. Mackinlay, Bailey A. T. Weatherbee, Viviane Souza Rosa, Charlotte E. Handford, George Hudson, Tim Coorens, Lygia Pereira, Sam Behjati, Ludovic Vallier, Marta N. Shahbazi, Magdalena Zernicka-Goetz
Summary: This study established conditions to differentiate human pluripotent stem cells into yolk sac-like cells and found that these cells can induce the expression of specific markers in human embryonic stem cells. The results suggest a crucial role of the yolk sac in epiblast cell fate specification in the human embryo.
Article
Cell & Tissue Engineering
Ranna El-Khairi, Evelyn Olszanowski, Daniele Muraro, Pedro Madrigal, Katarzyna Tilgner, Mariya Chhatriwala, Sapna Vyas, Crystal Y. Chia, Ludovic Vallier, Santiago A. Rodriguez-Segui
Summary: The study investigated the molecular mechanisms underlying HNF1B-associated diabetes using a human induced pluripotent stem cell model. It was found that HNF1B haploinsufficiency affects pancreatic progenitor cell differentiation and cell proliferation. By examining potential HNF1B gene targets, insights into the pathogenesis of the disease were provided.
Review
Endocrinology & Metabolism
Juan Ignacio Burgos, Ludovic Vallier, Santiago A. Rodriguez-Segui
Summary: Modeling monogenic diabetes using human pluripotent stem cells allows for detailed analysis of disease-associated gene regulatory mechanisms and has revealed new insights into the disease. This approach has the potential to improve understanding of monogenic diabetes pathogenesis and therapeutic strategies.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Cell & Tissue Engineering
Floris J. M. Roos, Gilles S. van Tienderen, Haoyu Wu, Ignacio Bordeu, Dina Vinke, Laura Munoz Albarinos, Kathryn Monfils, Sabrah Niesten, Ron Smits, Jorke Willemse, Oskar Rosmark, Gunilla Westergren-Thorsson, Daniel J. Kunz, Maurice de Wit, Pim J. French, Ludovic Vallier, Jan N. M. IJzermans, Richard Bartfai, Hendrik Marks, Ben D. Simons, Martin E. van Royen, Monique M. A. Verstegen, Luc J. W. van der Laan
Summary: Researchers have successfully established human branching cholangiocyte organoids, which can self-organize into complex tubular structures resembling intrahepatic bile ducts. These organoids show high similarity to primary cholangiocytes, and the branching growth process is dependent on JAG1/NOTCH2 signaling. When applied to cholangiocarcinoma tumor organoids, the branching cholangiocarcinoma organoids exhibit morphology and transcriptomic profile closer to primary tumors and increased chemoresistance.
Article
Biology
Rute A. Tomaz, Ekaterini D. Zacharis, Fabian Bachinger, Annabelle Wurmser, Daniel Yamamoto, Sandra Petrus-Reurer, Carola M. Morell, Dominika Dziedzicka, Brandon T. Wesley, Imbisaat Geti, Charis-Patricia Segeritz, Miguel C. de Brito, Mariya Chhatriwala, Daniel Ortmann, Kourosh Saeb-Parsy, Ludovic Vallier
Summary: Directed differentiation of human pluripotent stem cells into hepatocyte-like cells is a major challenge. Forward programming offers a versatile alternative to overcome the limitations and generate functional hepatocytes rapidly.
Article
Cell Biology
Brandon T. Wesley, Alexander D. B. Ross, Daniele Muraro, Zhichao Miao, Sarah Saxton, Rute A. Tomaz, Carola M. Morell, Katherine Ridley, Ekaterini D. Zacharis, Sandra Petrus-Reurer, Judith Kraiczy, Krishnaa T. Mahbubani, Stephanie Brown, Jose Garcia-Bernardo, Clara Alsinet, Daniel Gaffney, Dave Horsfall, Olivia C. Tysoe, Rachel A. Botting, Emily Stephenson, Dorin-Mirel Popescu, Sonya MacParland, Gary Bader, Ian D. McGilvray, Daniel Ortmann, Fotios Sampaziotis, Kourosh Saeb-Parsy, Muzlifah Haniffa, Kelly R. Stevens, Matthias Zilbauer, Sarah A. Teichmann, Ludovic Vallier
Summary: In this study, the developmental trajectories of human fetal liver cell types were described at single-cell resolution, and bipotential hepatoblast organoids were generated. This provides a platform for investigating human liver development and producing cell types for clinical applications.
NATURE CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Anna M. Speicher, Lisanne Korn, Julia Csatari, Laura Gonzalez-Cano, Michael Heming, Christian Thomas, Christina B. Schroeter, David Schafflick, Xiaolin Li, Lukas Gola, Alexander Engler, Thilo Kaehne, Ludovic Vallier, Sven G. Meuth, Gerd Meyer zu Horste, Stjepana Kovac, Heinz Wiendl, Hans R. Scholer, Matthias Pawlowski
Summary: This study presents a forward programming protocol for generating microglia-like cells from human pluripotent stem cells. The generated cells exhibit similar characteristics to native microglia on a morphological, transcriptional, and functional level. The protocol can be used for reductionist studies and complex coculture systems, including 3D brain organoids, to investigate cellular interactions in healthy and diseased environments.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Teresa Brevini, Mailis Maes, Gwilym J. Webb, Binu John, Claudia D. Fuchs, Gustav Buescher, Lu Wang, Chelsea Griffiths, Marnie L. Brown, William E. Scott, Pehuen Pereyra-Gerber, William T. H. Gelson, Stephanie Brown, Scott Dillon, Daniele Muraro, Jo Sharp, Megan Neary, Helen Box, Lee Tatham, James Stewart, Paul Curley, Henry Pertinez, Sally Forrest, Petra Mlcochova, Sagar S. Varankar, Mahnaz Darvish-Damavandi, Victoria L. Mulcahy, Rhoda E. Kuc, Thomas L. Williams, James A. Heslop, Davide Rossetti, Olivia C. Tysoe, Vasileios Galanakis, Marta Vila-Gonzalez, Thomas W. M. Crozier, Johannes Bargehr, Sanjay Sinha, Sara S. Upponi, Corrina Fear, Lisa Swift, Kourosh Saeb-Parsy, Susan E. Davies, Axel Wester, Hannes Hagstrom, Espen Melum, Darran Clements, Peter Humphreys, Jo Herriott, Edyta Kijak, Helen Cox, Chloe Bramwell, Anthony Valentijn, Christopher J. R. Illingworth, Bassam Dahman, Dustin R. Bastaich, Raphaella D. Ferreira, Thomas Marjot, Eleanor Barnes, Andrew M. Moon, Alfred S. Barritt, Ravindra K. Gupta, Stephen Baker, Anthony P. Davenport, Gareth Corbett, Vassilis G. Gorgoulis, Simon J. A. Buczacki, Joo-Hyeon Lee, Nicholas J. Matheson, Michael Trauner, Andrew J. Fisher, Paul Gibbs, Andrew J. Butler, Christopher J. E. Watson, George F. Mells, Gordon Dougan, Andrew Owen, Ansgar W. Lohse, Ludovic Vallier, Fotios Sampaziotis
Summary: Modulating the expression of angiotensin-converting enzyme 2 (ACE2) through farnesoid X receptor (FXR) can reduce susceptibility to SARS-CoV-2 infection, as shown in various tissues and organoids in vitro, in vivo, and ex vivo. The use of z-guggulsterone and ursodeoxycholic acid (UDCA) can downregulate ACE2 and decrease viral infection, including in the nasal epithelium. Clinical data also indicate positive outcomes with UDCA treatment in SARS-CoV-2 infection. These findings suggest that targeting the FXR-ACE2 pathway could be a potential strategy for preventing COVID-19.
Article
Multidisciplinary Sciences
Shota Nakanoh, Juned Kadiwala, Laetitia Pinte, Carola Maria Morell, An-Sofie Lenaerts, Ludovic Vallier
Summary: This study reveals the roles of RB proteins in maintaining and acquiring cell identities during early development, as well as their necessity in generating advanced derivatives after the formation of primary germ layers. The generated human embryonic stem cells lacking RB family proteins provide a useful tool to investigate the detailed molecular roles of RB family proteins in various cell types accessible from human pluripotent stem cells.
Article
Cell Biology
Walid Al-Akkad, Pilar Acedo, Maria-Giovanna Vilia, Luca Frenguelli, Alexander Ney, Irene Rodriguez-Hernandez, Peter L. Labib, Domenico Tamburrino, Gabriele Spoletini, Andrew R. Hall, Simone Canestrari, Anna Osnato, Jose Garcia-Bernardo, Leinal Sejour, Vessela Vassileva, Ioannis S. Vlachos, Giuseppe Fusai, Tu Vinh Luong, Steven R. Whittaker, Stephen P. Pereira, Ludovic Vallier, Massimo Pinzani, Krista Rombouts, Giuseppe Mazza
Summary: The tissue-matched human extracellular matrix (ECM) has a significant impact on driving the development of pancreatic ductal adenocarcinoma (PDAC) and promoting chemotherapy resistance, as revealed by this study. The 3D models provide a more reliable in vitro cell culture for primary and metastatic PDAC cells.
