Article
Biotechnology & Applied Microbiology
Elena F. Jacobson, Zijing Chen, Demetrios M. Stoukides, Gopika G. Nair, Matthias Hebrok, Emmanuel S. Tzanakakis
Summary: This study demonstrates successful expansion and directed differentiation of human pluripotent stem cells to definitive endoderm in a controlled stirred suspension bioreactor under xeno-free conditions. The cultures showed a significant increase in cell number while maintaining pluripotency and viability, with the differentiation efficiency of definitive endoderm cells consistently higher in the bioreactor compared to planar cultures. The tunable strategy established in this study is suitable for scalable manufacturing of definitive endoderm cells from different human pluripotent stem cell lines, advancing bioprocess development for a wide range of human definitive endoderm cell-derived therapeutics.
BIOTECHNOLOGY AND BIOENGINEERING
(2021)
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
Environmental Sciences
John T. Gamble, Kristen Hopperstad, Chad Deisenroth
Summary: Environmental chemical exposures play a significant role in infant health, and new methods have been developed to detect chemical risks. A model platform has been developed to rapidly identify potential developmental toxicants and understand their effects on early human development pathways and processes.
Article
Biochemical Research Methods
Julia Vallverdu, Raquel A. Martinez Garcia de la Torre, Inge Mannaerts, Stefaan Verhulst, Ayla Smout, Mar Coll, Silvia Arino, Teresa Rubio-Tomas, Beatriz Aguilar-Bravo, Celia Martinez-Sanchez, Delia Blaya, Catherine M. Verfaillie, Leo A. van Grunsven, Pau Sancho-Bru
Summary: Human iPSCs are differentiated into HSCs with growth factors for in vitro modeling. The protocol yields iPSC-HSCs with phenotypic and functional characteristics of primary HSCs, suitable for high-throughput in vitro studies. Coculturing iPSC-HSCs with hepatocytes allows for the formation of 3D hepatic spheroids, enabling modeling and drug screening studies.
Article
Cell Biology
Vivian Lu, Irena J. Roy, Alejandro Torres, James H. Joly, Fasih M. Ahsan, Nicholas A. Graham, Michael A. Teitell
Summary: This study reveals that, under exogenous glutamine withdrawal, ectoderm can generate sufficient glutamine to sustain cell viability and differentiation, while glutamine in mesoderm and endoderm is a preferred precursor of other compounds. The study also suggests that factors affecting germ layer differentiation may include specific glutamine enzyme gene expression patterns at the embryonic stage.
DEVELOPMENTAL CELL
(2022)
Article
Cell & Tissue Engineering
Ryota Yasui, Keisuke Sekine, Kiyoshi Yamaguchi, Yoichi Furukawa, Hideki Taniguchi
Summary: Efficient optimization of pluripotent stem cell differentiation protocols requires in-depth exploration of experimental methods, with statistical design playing a crucial role in improving screening efficiency. Robust parameter design can effectively facilitate research into optimizing various differentiation schemes.
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
Gastroenterology & Hepatology
Caitlin Peaslee, Cristina Esteva-Font, Tao Su, Antonio Munoz-Howell, Caroline C. Duwaerts, Zhe Liu, Sneha Rao, Ke Liu, Marisa Medina, Julie B. Sneddon, Jacquelyn J. Maher, Aras N. Mattis
Summary: The use of doxycycline significantly enhances the efficiency of iPSC differentiation into endoderm cells, promoting proliferation and inhibiting apoptosis. This method consistently generates complete endoderm sheets from a large number of iPSC lines, facilitating further differentiation and research.
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
Chemistry, Multidisciplinary
Deena Al Mahbuba, Sayaka Masuko, Shiwei Wang, Deepsing Syangtan, Jeong Seuk Kang, Yuefan Song, Tay Won Shin, Ke Xia, Fuming Zhang, Robert J. Linhardt, Edward S. Boyden, Laura L. Kiessling
Summary: Using expansion microscopy, researchers found that the nanotopography of heparan sulfate (HS) changes significantly during human pluripotent stem cell differentiation, and these changes are correlated with growth factor signaling. In undifferentiated cells, HS is densely distributed as hair-like protrusions, which can recruit fibroblast growth factor for signaling. However, during differentiation into ectodermal lineage, HS becomes localized into dispersed puncta, leading to a decrease in fibroblast growth factor binding to neural cells. This study highlights the importance of HS nanotopography in growth factor binding.
Article
Cell Biology
Jana Krueger, Markus Breunig, Lino Pascal Pasquini, Mareen Morawe, Alexander Gross, Frank Arnold, Ronan Russell, Thomas Seufferlein, Ninel Azoitei, Hans A. Kestler, Cecile Julier, Sandra Heller, Meike Hohwieler, Alexander Kleger
Summary: In this study, human pluripotent stem cells were used to identify novel genes involved in early endodermal development. The findings provide important insights into human development and disease models.
Article
Biochemistry & Molecular Biology
Carolina Villarroya-Beltri, Ana Filipa B. Martins, Alejandro Garcia, Daniel Gimenez, Eduardo Zarzuela, Monica Novo, Cristina Del Alamo, Jose Gonzalez-Martinez, Gloria C. Bonel-Perez, Irene Diaz, Maria Guillamot, Massimo Chiesa, Ana Losada, Osvaldo Grana-Castro, Meritxell Rovira, Javier Munoz, Maria Salazar-Roa, Marcos Malumbres
Summary: Maintenance of stemness is regulated by CDC14, a CDK-counteracting phosphatase, which dephosphorylates UTF1 to trigger its degradation and control neural differentiation. Lack of CDC14 results in deficient neural system development and impaired neural differentiation from ESCs. CDC14 phosphatases are critical molecular switches linking cell cycle regulation and self-renewal.
Article
Pharmacology & Pharmacy
Michelle Vanessa Kamga Kapchoup, Juergen Hescheler, Filomain Nguemo
Summary: Hydroxychloroquine (HDQ) has been widely studied for its potential use in the treatment and prevention of COVID-19. This antimalarial drug has shown beneficial effects on stem cell proliferation and cardiomyocyte activity, but it can also be toxic at high concentrations. Identifying risk factors and understanding the cardiotoxic profile of HDQ is challenging.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Eleanor Luce, Clara Steichen, Soumeya Abed, Anne Weber, Philippe Leboulch, Leila Maouche-Chretien, Anne Dubart-Kupperschmitt
Summary: The study demonstrates that siPSCs can differentiate into liver cells and self-organize into 3D structures, facilitating research on liver development and the development of co-culture systems.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell & Tissue Engineering
Finn J. Hawkins, Shingo Suzuki, Mary Lou Beermann, Cristina Barilla, Ruobing Wang, Carlos Villacorta-Martin, Andrew Berical, J. C. Jean, Jake Le Suer, Taylor Matte, Chantelle Simone-Roach, Yang Tang, Thorsten M. Schlaeger, Ana M. Crane, Nadine Matthias, Sarah X. L. Huang, Scott H. Randell, Joshua Wu, Jason R. Spence, Gianni Carraro, Barry R. Stripp, Andras Rab, Eric J. Sorsher, Amjad Horani, Steven L. Brody, Brian R. Davis, Darrell N. Kotton
Summary: The directed differentiation of human iPSCs into airway basal cells (iBCs) demonstrates the functional characteristics of airway basal cells and can be used to model characteristic changes in airway diseases.
Article
Chemistry, Multidisciplinary
Muhammad Rizwan, Ana Fokina, Tove Kivijarvi, Mina Ogawa, Markus Kufleitner, Onofrio Laselva, Laura J. Smith, Christine E. Bear, Shinichiro Ogawa, Gordon Keller, Molly S. Shoichet
Summary: Immobilizing jagged1 on chemically defined hyaluronan allows for specific differentiation of human embryonic stem cell-derived hepatoblasts to cholangiocytes, while a new strategy using photochemical methods achieves spatiotemporal control over Notch signaling for ultimate use in regenerative medicine strategies of the liver.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Cell & Tissue Engineering
Alexander A. Mikryukov, Amine Mazine, Bei Wei, Donghe Yang, Yifei Miao, Mingxia Gu, Gordon M. Keller
Summary: The embryonic endocardium plays a vital role in early heart development by inducing the formation of trabecular myocardium, the source of valvular cells and part of the coronary vasculature. Human endocardial cells offer unique therapeutic opportunities, such as engineering biological valves and cell-based therapy for damaged hearts. By generating hPSC-derived endothelial cells, key signaling pathways for the development of endocardial cells were identified, with a novel role for BMP10 in lineage specification.
Article
Oncology
Rokshana Stephny Geread, Abishika Sivanandarajah, Emily Rita Brouwer, Geoffrey A. Wood, Dimitrios Androutsos, Hala Faragalla, April Khademi
Summary: This study proposes a novel proliferation index (PI) calculator for Ki67 images called piNET, which was successfully tested on multiple datasets, showing consistent performance and high accuracy using deep learning technology. Several innovations, such as adapting to wide variability of medical images, training purely on tumor cells, weak supervision on learning background regions, and introducing hotspot analysis for automated scoring, contribute to the system's success in improving accuracy and efficiency.
Article
Cell Biology
Kim Wong, Latasha Ludwig, Oscar Krijgsman, David J. Adams, Geoffrey A. Wood, Louise van der Weyden
Summary: The study sequenced cancer genes in canine and feline hemangiosarcomas, showing they share genetic similarities with human angiosarcoma, including recurrent mutations in driver genes. Comparison analysis also revealed different mutational profiles in these tumors across tissue sites.
DISEASE MODELS & MECHANISMS
(2021)
Article
Pathology
Britta J. Knight, Geoffrey A. Wood, Robert A. Foster, Brenda L. Coomber
Summary: Mast cell tumors are common skin tumors in dogs, and grading is helpful for prognosis. This study found that Beclin-1 immunolabeling is higher in recurrent and metastatic tumors, and is predictive for survival after adjunctive treatment, especially in high-grade tumors. This may suggest a potential use of autophagy inhibitors to improve treatment response in high-grade MCTs.
VETERINARY PATHOLOGY
(2022)
Article
Multidisciplinary Sciences
Amanda W. K. AuYeung, Robert C. Mould, Ashley A. Stegelmeier, Jacob P. van Vloten, Khalil Karimi, J. Paul Woods, James J. Petrik, Geoffrey A. Wood, Byram W. Bridle
Summary: Vaccination against oncolytic vesicular stomatitis virus-encoded tumor antigen for melanoma treatment did not abrogate oncolysis even when a VSV-vectored booster vaccine was administered at the peak of the primary effector T cell response. In a murine melanoma model, it was found that tumor-infiltrating T cells had reduced cytopathic potential due to immunosuppression, and virus-induced lymphopenia acutely removed virus-specific T cells from tumors, enabling the retention of oncolysis.
SCIENTIFIC REPORTS
(2021)
Article
Cardiac & Cardiovascular Systems
Wahiba Dhahri, Tamilla Sadikov Valdman, Dan Wilkinson, Elizabeth Pereira, Eylul Ceylan, Naaz Andharia, Beiping Qiang, Hassan Masoudpour, Fanny Wulkan, Elya Quesnel, Wenlei Jiang, Shunsuke Funakoshi, Amine Mazine, M. Juliana Gomez-Garcia, Neda Latifi, Yidi Jiang, Ella Huszti, Craig A. Simmons, Gordon Keller, Michael A. Laflamme
Summary: The study showed that culturing hPSC-CMs on PDMS-lined roller bottles and transplanting these cells into a guinea pig model of myocardial infarction resulted in better structural and functional outcomes compared to conventional immature hPSC-CM populations. The PDMS-matured hPSC-CMs exhibited increased cardiac gene expression and more mature properties in vitro, and the intracardiac grafts formed with these cells showed enhanced structure and alignment, better electromechanical integration, and improved contractile function. This study provides practical methods for the scaled generation of mature hPSC-CMs and highlights the importance of using more mature cardiomyocytes for cardiac regeneration.
Article
Veterinary Sciences
Christopher J. Pinard, Ashley A. Stegelmeier, Byram W. Bridle, Anthony J. Mutsaers, R. Darren Wood, Geoffrey A. Wood, J. Paul Woods, Samuel E. Hocker
Summary: This study found that expression of PD-1 on CD8(+) lymphocytes in urine samples of canine UC patients was significantly elevated, and the CD4:CD8 ratio and CD8:Treg ratio in urine did not show significant variation compared to healthy dogs. Additionally, cystitis patients had significantly higher levels of CD4(+) T cells, CD8(+) T cells, and Tregs in their blood samples compared to both UC patients and healthy dogs. Cytokine analysis showed significant elevations in various urinary cytokines in UC patients, some of which have been correlated with lymphocyte-specific PD-1 expression in human muscle-invasive urothelial carcinoma.
VETERINARY AND COMPARATIVE ONCOLOGY
(2022)
Article
Immunology
Christopher J. Pinard, Samuel E. Hocker, Andrew C. Poon, Jordon M. Inkol, Arata Matsuyama, R. Darren Wood, Geoffrey A. Wood, J. Paul Woods, Anthony J. Mutsaers
Summary: This study evaluated the protein and mRNA expression of PD-1 and PD-L1 in three established canine urothelial carcinoma cell lines and found varying degrees of expression. Flow cytometry analysis revealed higher cell intrinsic PD-1 expression in these cell lines. Further research is needed to determine the potential of immunotherapy targeting PD-1 and PD-L1 in canine UC.
VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY
(2022)
Article
Oncology
Robert C. Mould, Jacob P. van Vloten, Amanda W. K. AuYeung, Scott R. Walsh, Jondavid de Jong, Leonardo Susta, Anthony J. Mutsaers, James J. Petrik, Geoffrey A. Wood, Sarah K. Wootton, Khalil Karimi, Byram W. Bridle
Summary: The study aimed to induce anti-tumor immune responses through a vaccine strategy targeting survivin, but failed to detect survivin-specific T cell responses in mice, suggesting unusually robust tolerance to survivin in commonly used mouse strains. The vaccination method shows promise for identifying novel and subdominant T cell epitopes.
Review
Veterinary Sciences
Anita K. Luu, Geoffrey A. Wood, Alicia M. Viloria-Petit
Summary: Canine osteosarcoma is an aggressive malignancy with a lack of reliable biomarkers in clinical practice, making it difficult to diagnose and treat effectively. This review summarizes explored biomarkers in canine osteosarcoma, focusing on molecular markers in tumor samples and emerging liquid biomarkers in blood-based biopsies.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Article
Cell Biology
Blair K. Gage, Simone Merlin, Cristina Olgasi, Antonia Follenzi, Gordon M. Keller
Summary: This study develops an efficient method to generate human pluripotent stem cell-derived liver sinusoidal endothelial cell (LSEC) progenitors from specific mesoderm sub-populations. The study shows that venous endothelial cells generated from certain mesoderm sub-populations are more efficient in LSEC engraftment and can secrete bioactive coagulation factor VIII. These findings highlight the importance of mesoderm induction in generating functional LSECs.
Article
Cell & Tissue Engineering
Yasaman Aghazadeh, Farida Sarangi, Frankie Poon, Blessing Nkennor, Emily C. McGaugh, Sara S. Nunes, M. Cristina Nostro
Summary: Pancreatic progenitor cells derived from human pluripotent stem cells can be purified using glycoprotein 2 enrichment, leading to the generation of functional beta cells and reducing the risk of teratomas.
Article
Cell & Tissue Engineering
Donghe Yang, Juliana Gomez-Garcia, Shunsuke Funakoshi, Thinh Tran, Ian Fernandes, Gary D. Bader, Michael A. Laflamme, Gordon M. Keller
Summary: This study models human heart development using human pluripotent stem cells, revealing the differentiation and progression of different cardiac lineages. The findings demonstrate the conservation of cardiac lineage development between humans and mice, providing important resources for establishing disease models and developing new therapies.
Article
Veterinary Sciences
Bactelius Turicea, Chantale L. Pinard, Emily R. Brouwer, Stephane Lair, Geoffrey A. Wood, Marie-Odile Benoit-Biancamano
Summary: This study described the histological and histochemical characteristics of the lacrimal glands of beluga whales. The findings showed that the lacrimal glands of beluga whales have similar features to those of artiodactyla and carnivora orders.
CANADIAN JOURNAL OF VETERINARY RESEARCH-REVUE CANADIENNE DE RECHERCHE VETERINAIRE
(2022)
