Browsing by Author "Wang, Juan"

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    Platelets in Alcohol-Associated Liver Disease: Interaction With Neutrophils
    (Elsevier, 2024) Wang, Juan; Wang, Xianda; Peng, Haodong; Dong, Zijian; Liangpunsakul, Suthat; Zuo, Li; Wang, Hua; Medicine, School of Medicine
    Alcohol-associated liver disease (ALD) is a major contributor to liver-related mortality globally. An increasing body of evidence underscores the pivotal role of platelets throughout the spectrum of liver injury and recovery, offering unique insights into liver homeostasis and pathobiology. Alcoholic-associated steatohepatitis is characterized by the infiltration of hepatic neutrophils. Recent studies have highlighted the extensive distance neutrophils travel through sinusoids to reach the liver injury site, relying on a platelet-paved endothelium for efficient crawling. The adherence of platelets to neutrophils is crucial for accurate migration from circulation to the inflammatory site. A gradual decline in platelet levels leads to diminished neutrophil recruitment. Platelets exhibit the ability to activate neutrophils. Platelet activation is heightened upon the release of platelet granule contents, which synergistically activate neutrophils through their respective receptors. The sequence culminates in the formation of platelet–neutrophil complexes and the release of neutrophil extracellular traps intensifies liver damage, fosters inflammatory immune responses, and triggers hepatotoxic processes. Neutrophil infiltration is a hallmark of alcohol-associated steatohepatitis, and the roles of neutrophils in ALD pathogenesis have been studied extensively, however, the involvement of platelets in ALD has received little attention. The current review consolidates recent findings on the intricate and diverse roles of platelets and neutrophils in liver pathophysiology and in ALD. Potential therapeutic strategies are highlighted, focusing on targeting platelet–neutrophil interactions and activation in ALD. The anticipation is that innovative methods for manipulating platelet and neutrophil functions will open promising avenues for future ALD therapy.
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    A Pulmonary Vascular Model From Endothelialized Whole Organ Scaffolds
    (Frontiers Media, 2021-11-19) Yuan, Yifan; Leiby, Katherine L.; Greaney, Allison M.; Brickman Raredon, Micha Sam; Qian, Hong; Schupp, Jonas C.; Engler, Alexander J.; Baevova, Pavlina; Adams, Taylor S.; Kural, Mehmet H.; Wang, Juan; Obata, Tomohiro; Yoder, Mervin C.; Kaminski, Naftali; Niklason, Laura E.; Pediatrics, School of Medicine
    The development of an in vitro system for the study of lung vascular disease is critical to understanding human pathologies. Conventional culture systems fail to fully recapitulate native microenvironmental conditions and are typically limited in their ability to represent human pathophysiology for the study of disease and drug mechanisms. Whole organ decellularization provides a means to developing a construct that recapitulates structural, mechanical, and biological features of a complete vascular structure. Here, we developed a culture protocol to improve endothelial cell coverage in whole lung scaffolds and used single-cell RNA-sequencing analysis to explore the impact of decellularized whole lung scaffolds on endothelial phenotypes and functions in a biomimetic bioreactor system. Intriguingly, we found that the phenotype and functional signals of primary pulmonary microvascular revert back-at least partially-toward native lung endothelium. Additionally, human induced pluripotent stem cell-derived endothelium cultured in decellularized lung systems start to gain various native human endothelial phenotypes. Vascular barrier function was partially restored, while small capillaries remained patent in endothelial cell-repopulated lungs. To evaluate the ability of the engineered endothelium to modulate permeability in response to exogenous stimuli, lipopolysaccharide (LPS) was introduced into repopulated lungs to simulate acute lung injury. After LPS treatment, proinflammatory signals were significantly increased and the vascular barrier was impaired. Taken together, these results demonstrate a novel platform that recapitulates some pulmonary microvascular functions and phenotypes at a whole organ level. This development may help pave the way for using the whole organ engineering approach to model vascular diseases.
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    Readily Available Tissue-Engineered Vascular Grafts Derived From Human Induced Pluripotent Stem Cells
    (American Heart Association, 2022) Luo, Jiesi; Qin, Lingfeng; Park, Jinkyu; Kural, Mehmet H.; Huang, Yan; Shi, Xiangyu; Riaz, Muhammad; Wang, Juan; Ellis, Matthew W.; Anderson, Christopher W.; Yuan, Yifan; Ren, Yongming; Yoder, Mervin C.; Tellides, George; Niklason, Laura E.; Qyang, Yibing; Pediatrics, School of Medicine