Modeling Transient Abnormal Myelopoiesis Using Induced Pluripotent Stem Cells and CRISPR/Cas9 Technology

Scientists employed disease modeling in vitro by the use of customizable induced pluripotent stem cells to generate a transient abnormal myelopoiesis model.
[Molecular Therapy-Methods & Clinical Development]
Barwe, S. P., Sidhu, I., Kolb, E. A., & Gopalakrishnapillai, A. (2020). Modeling transient abnormal myelopoiesis using induced pluripotent stem cells and CRISPR/Cas9 technology. Molecular Therapy - Methods & Clinical Development, 0(0). https://doi.org/10.1016/j.omtm.2020.09.007 Cite
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HDAC6 Is Critical for Ketamine-Induced Impairment of Dendritic and Spine growth in GABAergic projection neurons

Investigators used a human iPSC-derived striatal GABA neuron system to investigate the effects of ketamine on histone deacetylase 6 (HDAC6) and the morphological development of medium spiny neurons.
[Acta Pharmacologica Sinica]
Li, X., Saiyin, H., Zhou, J., Yu, Q., & Liang, W. (2020). HDAC6 is critical for ketamine-induced impairment of dendritic and spine growth in GABAergic projection neurons. Acta Pharmacologica Sinica, 1–10. https://doi.org/10.1038/s41401-020-00521-3 Cite
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Reprogramming Roadmap Reveals Route to Human Induced Trophoblast Stem Cells

Scientists reconstructed molecular reprogramming trajectories of human dermal fibroblasts using single-cell transcriptomics. This revealed that reprogramming into primed and naive pluripotency followed diverging and distinct trajectories.
[Nature]
Liu, X., Ouyang, J. F., Rossello, F. J., Tan, J. P., Davidson, K. C., Valdes, D. S., Schröder, J., Sun, Y. B. Y., Chen, J., Knaupp, A. S., Sun, G., Chy, H. S., Huang, Z., Pflueger, J., Firas, J., Tano, V., Buckberry, S., Paynter, J. M., Larcombe, M. R., … Polo, J. M. (2020). Reprogramming roadmap reveals route to human induced trophoblast stem cells. Nature, 1–7. https://doi.org/10.1038/s41586-020-2734-6 Cite
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Nicotinamide Restricts Neural Precursor Proliferation to Enhance Catecholaminergic Neuronal Subtype Differentiation from Mouse Embryonic Stem Cells

Researchers investigated the ability of nicotinamide to promote the development of mature catecholaminergic neuronal populations (associated with Parkinson’s disease) from mouse ESCs, as well as investigating the underlying mechanisms of nicotinamide’s action.
[PLoS One]
Griffin, S. M., Pickard, M. R., Hawkins, C. P., Williams, A. C., & Fricker, R. A. (2020). Nicotinamide restricts neural precursor proliferation to enhance catecholaminergic neuronal subtype differentiation from mouse embryonic stem cells. PLOS ONE, 15(9), e0233477. https://doi.org/10.1371/journal.pone.0233477 Cite
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iPSC-Derived Endothelial Networks Accelerate Vascularization but Not Bone Regeneration

Vascular networks were generated from endothelial cells (ECs) derived from human iPSCs. Network formation by iPSC-ECs within fibrin gels was investigated in a mesenchymal stem cell co-culture spheroid model.
[Tissue Engineering]
Roux, B. M., Vaicik, M., Shrestha, B., Montelongo, S., Stojkova, K., Yang, F., Guda, T., Cinar, A., & Brey, E. M. (2020). iPSC-derived endothelial networks accelerate vascularization but not bone regeneration. Tissue Engineering Part A. https://doi.org/10.1089/ten.TEA.2020.0200 Cite
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Century Therapeutics Announces Appointment of Michael C. Diem as Chief Business Officer

Century Therapeutics, developer of iPSC-derived allogeneic cell therapies for cancer, has announced the appointment of Michael C. Diem, MD, as Chief Business Officer. Dr. Diem has more than 15 years of experience in the global pharmaceutical and biotech industries and nearly 10 years of experience in academic and clinical medicine.
[Century Therapeutics (Business Wire, Inc.)]
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Curi Bio Launches ComboMat Platform for iPSC-Based Drug Discovery

Curi Bio has announced the ComboMat™ platform, a proprietary human iPSC-derived cardiomyocyte maturation technology. Curi’s ComboMat platform leverages a combination of cues—including a proprietary microRNA cocktail—to drive the functional development and maturation of cardiomyocytes with applications in drug discovery, disease modeling, and safety and efficacy screening.
[Curi Bio]
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Polygenic Architecture Informs Potential Vulnerability to Drug-Induced Liver Injury

The polygenic risk score predicted the susceptibility to drug-induced liver injury in patients treated with fasiglifam, amoxicillin–clavulanate or flucloxacillin and in primary hepatocytes and stem cell-derived organoids from multiple donors treated with over ten different drugs.
[Nature Medicine]
Koido, M., Kawakami, E., Fukumura, J., Noguchi, Y., Ohori, M., Nio, Y., Nicoletti, P., Aithal, G. P., Daly, A. K., Watkins, P. B., Anayama, H., Dragan, Y., Shinozawa, T., & Takebe, T. (2020). Polygenic architecture informs potential vulnerability to drug-induced liver injury. Nature Medicine, 1–8. https://doi.org/10.1038/s41591-020-1023-0 Cite
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Production, Safety and Efficacy of iPSC-Derived Mesenchymal Stromal Cells in Acute Steroid-Resistant Graft versus Host Disease: A Phase I, Multicenter, Open-Label, Dose-Escalation Study

Researchers assessed the safety and tolerability of CYP-001 (iPSC-derived MSCs), while the secondary objectives were to evaluate efficacy based on the proportion of participants who showed a complete response , overall response and overall survival by days 28/100.
[Nature Medicine]
Bloor, A. J. C., Patel, A., Griffin, J. E., Gilleece, M. H., Radia, R., Yeung, D. T., Drier, D., Larson, L. S., Uenishi, G. I., Hei, D., Kelly, K., Slukvin, I., & Rasko, J. E. J. (2020). Production, safety and efficacy of iPSC-derived mesenchymal stromal cells in acute steroid-resistant graft versus host disease: a phase I, multicenter, open-label, dose-escalation study. Nature Medicine, 1–6. https://doi.org/10.1038/s41591-020-1050-x Cite
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A Bilateral Tumor Model Identifies Transcriptional Programs Associated with Patient Response to Immune Checkpoint Blockade

Researchers introduced a resection and response-assessment approach for studying the tumor microenvironment before or shortly after treatment initiation to identify predictive biomarkers differentiating responders from nonresponders.
[Proceedings of the National Academy of Sciences of the United States of America]
Chen, I. X., Newcomer, K., Pauken, K. E., Juneja, V. R., Naxerova, K., Wu, M. W., Pinter, M., Sen, D. R., Singer, M., Sharpe, A. H., & Jain, R. K. (2020). A bilateral tumor model identifies transcriptional programs associated with patient response to immune checkpoint blockade. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2002806117 Cite
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Let-7 Derived from Endometrial Extracellular Vesicles is an Important Inducer of Embryonic Diapause in Mice

Scientists demonstrated that overexpression of microRNA let-7a or incubation with let-7g–enriched extracellular vesicles from endometrial epithelial cells prolonged the in vitro survival of mouse blastocysts, which developed into live pups after having been transferred to foster mothers.
[Science Advances]
Liu, W. M., Cheng, R. R., Niu, Z. R., Chen, A. C., Ma, M. Y., Li, T., Chiu, P. C., Pang, R. T., Lee, Y. L., Ou, J. P., Yao, Y. Q., & Yeung, W. S. B. (2020). Let-7 derived from endometrial extracellular vesicles is an important inducer of embryonic diapause in mice. Science Advances, 6(37), eaaz7070. https://doi.org/10.1126/sciadv.aaz7070 Cite
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