A Microscale Human Liver Platform that Supports the Hepatic Stages of Plasmodium falciparum and vivax by March-Riera, Sandra, Ng, Shengyong, Velmurugan, Soundarapandian, Galstian, Ani, Shan, Jing, Logan, David J., Carpenter, Anne E., Thomas, David, Sim, B. Kim Lee, Mota, Maria M., Hoffman, Stephen L.

“…Here, we establish the liver stages for both Plasmodium falciparum and Plasmodium vivax in a microscale human liver platform composed of cryopreserved, micropatterned human primary hepatocytes surrounded by supportive stromal cells. …”
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In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease by Stevens, Kelly R., Scull, Margaret A., Ramanan, Vyas, Fortin, Chelsea L., Chaturvedi, Ritika R., Knouse, Kristin Ann, Xiao, Jing W., Fung, Canny, Mirabella, Teodelinda, Chen, Amanda X., McCue, Margaret Grace, Yang, Michael T., Fleming, Heather, Chung, Kwanghun, de Jong, Ype P., Chen, Christopher S., Rice, Charles M., Bhatia, Sangeeta N

“…There was a concomitant increase in graft function as indicated by the production of multiple human liver proteins. Histologically, we observed the emergence of characteristic liver stereotypical microstructures mediated by coordinated growth of hepatocytes in close juxtaposition with a perfused vasculature. …”
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In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease by Stevens, Kelly R., Scull, Margaret A., Ramanan, Vyas, Fortin, Chelsea L., Chaturvedi, Ritika R., Knouse, Kristin Ann, Xiao, Jing W., Fung, Canny, Mirabella, Teodelinda, Chen, Amanda X., McCue, Margaret Grace, Yang, Michael T., Fleming, Heather, Chung, Kwanghun, de Jong, Ype P., Chen, Christopher S., Rice, Charles M., Bhatia, Sangeeta N

“…There was a concomitant increase in graft function as indicated by the production of multiple human liver proteins. Histologically, we observed the emergence of characteristic liver stereotypical microstructures mediated by coordinated growth of hepatocytes in close juxtaposition with a perfused vasculature. …”
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Improving Drug Discovery by Nucleic Acid Delivery in Engineered Human Microlivers by Mancio Silva, Liliana, Fleming, Heather, Miller, Alex B, Milstein, Stuart, Liebow, Abigail, Haslett, Patrick, Sepp-Lorenzino, Laura, Bhatia, Sangeeta N

“…Additionally, we apply this engineered platform to test siRNAs designed to target hepatocytes and impact human liver genetic and infectious diseases. Mancio-Silva et al. show that nucleic acid-mediated silencing of primary human hepatocytes can be leveraged in an in vitro engineered human liver model to fine-tune metabolism and to assess safety and efficacy of RNAi-based therapeutics.…”
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Adenovirus-Mediated Somatic Genome Editing of Pten by CRISPR/Cas9 in Mouse Liver in Spite of Cas9-Specific Immune Responses by Wang, Dan, Mou, Haiwei, Li, Shaoyong, Li, Yingxiang, Hough, Soren, Tran, Karen, Li, Jia, Sontheimer, Erik J., Weng, Zhiping, Gao, Guangping, Xue, Wen, Yin, Hao, Anderson, Daniel Griffith

“…Nonalcoholic steatohepatitis (NASH) is a prevalent human liver disease characterized by excessive fat accumulation in the liver. …”
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Expansion, in vivo–ex vivo cycling, and genetic manipulation of primary human hepatocytes by Michailidis, Eleftherios, Vercauteren, Koen, Mancio-Silva, Liliana, Andrus, Linda, Jahan, Cyprien, Ricardo-Lax, Inna, Zou, Chenhui, Kabbani, Mohammad, Park, Paul, Quirk, Corrine, Pyrgaki, Christina, Razooky, Brandon, Verhoye, Lieven, Zoluthkin, Irene, Lu, Wei-Yu, Forbes, Stuart J, Chiriboga, Luis, Theise, Neil D, Herzog, Roland W, Suemizu, Hiroshi, Schneider, William M, Shlomai, Amir, Meuleman, Philip, Bhatia, Sangeeta N, Rice, Charles M, de Jong, Ype P

“…Together, these advances provide flexible tools for the study of human liver disease and evaluation of hepatocytetargeted gene therapy approaches.…”
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A single-cell liver atlas of Plasmodium vivax infection by Mancio-Silva, Liliana, Gural, Nil, Real, Eliana, Wadsworth, Marc H, Butty, Vincent L, March, Sandra, Nerurkar, Niketa, Hughes, Travis K, Roobsoong, Wanlapa, Fleming, Heather E, Whittaker, Charlie A, Levine, Stuart S, Sattabongkot, Jetsumon, Shalek, Alex K, Bhatia, Sangeeta N

“…Malaria-causing Plasmodium vivax parasites can linger in the human liver for weeks to years and reactivate to cause recurrent blood-stage infection. …”
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In Vitro Culture, Drug Sensitivity, and Transcriptome of Plasmodium Vivax Hypnozoites by Gural, Nil, Mancio Silva, Liliana, Miller, Alex B, Galstian, Ani, Butty, Vincent L, Levine, Stuart S, Patrapuvich, Rapatbhorn, Desai, Salil P, Mikolajczak, Sebastian A, Kappe, Stefan H. I., Fleming, Heather, March-Riera, Sandra, Sattabongkot, Jetsumon, Bhatia, Sangeeta N

“…Plasmodium vivax hypnozoites are difficult to study due to the lack of human liver platforms. Gural et al. recapitulated the entire liver stage of P. vivax in vitro, including formation and reactivation of hypnozoites and release of merosomes. …”
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Hypoxia promotes liver stage malaria infection in primary human hepatocytes in vitro by Ng, Shengyong, March-Riera, Sandra, Galstian, Ani, Hanson, Kirsten, Carvalho, Tania, Mota, Maria M., Bhatia, Sangeeta N

“…We developed a microscale human liver platform comprised of precisely patterned primary human hepatocytes and nonparenchymal cells (MPCC) to model liver stage malaria, but the oxygen concentrations are typically higher in the in vitro liver platform than anywhere along the hepatic sinusoid. …”
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A Plasmodium berghei sporozoite-based vaccination platform against human malaria by Mendes, Antonio M., Machado, Marta, Goncalves-Rosa, Nataniel, Reuling, Isaie J., Foquet, Lander, Marques, Claudia, Salman, Ahmed M., Yang, Annie S. P., Moser, Kara A., Dwivedi, Ankit, Hermsen, Cornelus C., Jimenez-Diaz, Belen, Viera, Sara, Santos, Jorge M., Albuquerque, Ines, Bhatia, Sangeeta N, Bial, John, Angulo-Barturen, Anigo, Silva, Joana C., Leroux-Roels, Geert, Janse, Chris J., Khan, Shahid M., Mota, Maria M., Sauerwein, Robert W., Prudencio, Miguel

“…In a rabbit model, similarly susceptible to Pb hepatic but not blood infection, we show that PbVac elicits cross-species cellular immune responses, as well as PfCS-specific antibodies that efficiently inhibit Pf sporozoite liver invasion in human hepatocytes and in mice with humanized livers. Thus, PbVac is safe and induces functional immune responses in preclinical studies, warranting clinical testing and development.…”
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