Browsing by Subject "Directed differentiation"

Now showing 1 - 2 of 2
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    Engineering chimeric antigen receptor neutrophils from human pluripotent stem cells for targeted cancer immunotherapy
    (Cell Press, 2022) Chang, Yun; Syahirah, Ramizah; Wang, Xuepeng; Jin, Gyuhyung; Torregrosa-Allen, Sandra; Elzey, Bennett D.; Hummel, Sydney N.; Wang, Tianqi; Li, Can; Lian, Xiaojun; Deng, Qing; Broxmeyer, Hal E.; Bao, Xiaoping; Microbiology and Immunology, School of Medicine
    Neutrophils, the most abundant white blood cells in circulation, are closely related to cancer development and progression. Healthy primary neutrophils present potent cytotoxicity against various cancer cell lines through direct contact and via generation of reactive oxygen species. However, due to their short half-life and resistance to genetic modification, neutrophils have not yet been engineered with chimeric antigen receptors (CARs) to enhance their antitumor cytotoxicity for targeted immunotherapy. Here, we genetically engineered human pluripotent stem cells with synthetic CARs and differentiated them into functional neutrophils by implementing a chemically defined platform. The resulting CAR neutrophils present superior and specific cytotoxicity against tumor cells both in vitro and in vivo. Collectively, we established a robust platform for massive production of CAR neutrophils, paving the way to myeloid cell-based therapeutic strategies that would boost current cancer-treatment approaches.
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    Investigating pediatric disorders with induced pluripotent stem cells
    (Springer Nature, 2018-10) Durbin, Matthew D.; Cadar, Adrian G.; Chun, Young W.; Hong, Charles C.; Pediatrics, School of Medicine
    The study of disease pathophysiology has long relied on model systems, including animal models and cultured cells. In 2006, Shinya Yamanaka achieved a breakthrough by reprogramming somatic cells into induced pluripotent stem cells (iPSCs). This revolutionary discovery provided new opportunities for disease modeling and therapeutic intervention. With established protocols, investigators can generate iPSC lines from patient blood, urine, and tissue samples. These iPSCs retain ability to differentiate into every human cell type. Advances in differentiation and organogenesis move cellular in vitro modeling to a multicellular model capable of recapitulating physiology and disease. Here, we discuss limitations of traditional animal and tissue culture models, as well as the application of iPSC models. We highlight various techniques, including reprogramming strategies, directed differentiation, tissue engineering, organoid developments, and genome editing. We extensively summarize current established iPSC disease models that utilize these techniques. Confluence of these technologies will advance our understanding of pediatric diseases and help usher in new personalized therapies for patients.