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1. Isolation of Diverse Simian Arteriviruses Causing Hemorrhagic Disease

Author

Shaw, Teressa M., Dettle, Samuel T., Mejia, Andres, Hayes, Jennifer M., Simmons, Heather A., Basu, Puja, Kuhn, Jens H., Ramuta, Mitchell D., Warren, Cody J., Jahrling, Peter B., O'Connor, David H., Huang, Liupei, Zaeem, Misbah, Seo, Jiwon, Slukvin, Igor I., Brown, Matthew E., and Bailey, Adam L.

Subjects
United States. National Institutes of Health, Hemorrhagic fever, Ethylenediaminetetraacetic acid, Hematopoietic stem cells, Macrophages, Health, University of Wisconsin-Madison. Wisconsin National Primate Research Center
Abstract

Simarteriviruses (order Nidovirales, family Arteriviridae, subfamily Simarterivirinae) are genetically diverse viruses that naturally infect cercopithecoid monkeys throughout sub-Saharan Africa. Many divergent simarteriviruses can infect macaques, although severity of disease ranges [...]

Published
2024
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2. Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques.

Author

Nguyen, Sydney M, Antony, Kathleen M, Dudley, Dawn M, Kohn, Sarah, Simmons, Heather A, Wolfe, Bryce, Salamat, M Shahriar, Teixeira, Leandro BC, Wiepz, Gregory J, Thoong, Troy H, Aliota, Matthew T, Weiler, Andrea M, Barry, Gabrielle L, Weisgrau, Kim L, Vosler, Logan J, Mohns, Mariel S, Breitbach, Meghan E, Stewart, Laurel M, Rasheed, Mustafa N, Newman, Christina M, Graham, Michael E, Wieben, Oliver E, Turski, Patrick A, Johnson, Kevin M, Post, Jennifer, Hayes, Jennifer M, Schultz-Darken, Nancy, Schotzko, Michele L, Eudailey, Josh A, Permar, Sallie R, Rakasz, Eva G, Mohr, Emma L, Capuano, Saverio, Tarantal, Alice F, Osorio, Jorge E, O'Connor, Shelby L, Friedrich, Thomas C, O'Connor, David H, and Golos, Thaddeus G

Subjects
Lung, Decidua, Spleen, Amniotic Fluid, Umbilical Cord, Fetus, Placenta, Animals, Macaca mulatta, Humans, Pregnancy Complications, Infectious, Viremia, Disease Models, Animal, RNA, Viral, Fetal Development, Pregnancy, Female, Infectious Disease Transmission, Vertical, Zika Virus, Zika Virus Infection, Disease Models, Animal, Infectious Disease Transmission, Vertical, Pregnancy Complications, Infectious, RNA, Viral, Virology, Microbiology, Immunology, Medical Microbiology
Abstract

Infection with Zika virus (ZIKV) is associated with human congenital fetal anomalies. To model fetal outcomes in nonhuman primates, we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques. While non-pregnant animals in a previous study contemporary with the current report clear viremia within 10-12 days, maternal viremia was prolonged in 3 of 4 pregnancies. Fetal head growth velocity in the last month of gestation determined by ultrasound assessment of head circumference was decreased in comparison with biparietal diameter and femur length within each fetus, both within normal range. ZIKV RNA was detected in tissues from all four fetuses at term cesarean section. In all pregnancies, neutrophilic infiltration was present at the maternal-fetal interface (decidua, placenta, fetal membranes), in various fetal tissues, and in fetal retina, choroid, and optic nerve (first trimester infection only). Consistent vertical transmission in this primate model may provide a platform to assess risk factors and test therapeutic interventions for interruption of fetal infection. The results may also suggest that maternal-fetal ZIKV transmission in human pregnancy may be more frequent than currently appreciated.

Published
2017

4. Previous exposure to dengue virus is associated with increased Zika virus burden at the maternal-fetal interface in rhesus macaques

Author

Crooks, Chelsea M., primary, Weiler, Andrea M., additional, Rybarczyk, Sierra L., additional, Bliss, Mason I., additional, Jaeger, Anna S., additional, Murphy, Megan E., additional, Simmons, Heather A., additional, Mejia, Andres, additional, Fritsch, Michael K., additional, Hayes, Jennifer M., additional, Eickhoff, Jens C., additional, Mitzey, Ann M., additional, Razo, Elaina, additional, Braun, Katarina M., additional, Brown, Elizabeth A., additional, Yamamoto, Keisuke, additional, Shepherd, Phoenix M., additional, Possell, Amber, additional, Weaver, Kara, additional, Antony, Kathleen M., additional, Morgan, Terry K., additional, Newman, Christina M., additional, Dudley, Dawn M., additional, Schultz-Darken, Nancy, additional, Peterson, Eric, additional, Katzelnick, Leah C., additional, Balmaseda, Angel, additional, Harris, Eva, additional, O’Connor, David H., additional, Mohr, Emma L., additional, Golos, Thaddeus G., additional, Friedrich, Thomas C., additional, and Aliota, Matthew T., additional

Published
2021
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5. African-Lineage Zika Virus Replication Dynamics and Maternal-Fetal Interface Infection in Pregnant Rhesus Macaques

Author

Crooks, Chelsea M., primary, Weiler, Andrea M., additional, Rybarczyk, Sierra L., additional, Bliss, Mason, additional, Jaeger, Anna S., additional, Murphy, Megan E., additional, Simmons, Heather A., additional, Mejia, Andres, additional, Fritsch, Michael K., additional, Hayes, Jennifer M., additional, Eickhoff, Jens C., additional, Mitzey, Ann M., additional, Razo, Elaina, additional, Braun, Katarina M., additional, Brown, Elizabeth A., additional, Yamamoto, Keisuke, additional, Shepherd, Phoenix M., additional, Possell, Amber, additional, Weaver, Kara, additional, Antony, Kathleen M., additional, Morgan, Terry K., additional, Zeng, Xiankun, additional, Dudley, Dawn M., additional, Peterson, Eric, additional, Schultz-Darken, Nancy, additional, O’Connor, David H., additional, Mohr, Emma L., additional, Golos, Thaddeus G., additional, Aliota, Matthew T., additional, and Friedrich, Thomas C., additional

Published
2021
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7. African-lineage Zika virus replication dynamics and maternal-fetal interface infection in pregnant rhesus macaques

Author

Crooks, Chelsea M., primary, Weiler, Andrea M., additional, Rybarczyk, Sierra L., additional, Bliss, Mason, additional, Jaeger, Anna S., additional, Murphy, Megan E., additional, Simmons, Heather A., additional, Mejia, Andres, additional, Fritsch, Michael K., additional, Hayes, Jennifer M., additional, Eickhoff, Jens C., additional, Mitzey, Ann M., additional, Razo, Elaina, additional, Braun, Katarina M., additional, Brown, Elizabeth A., additional, Yamamoto, Keisuke, additional, Shepherd, Phoenix M., additional, Possell, Amber, additional, Weaver, Kara, additional, Antony, Kathleen M., additional, Morgan, Terry K., additional, Dudley, Dawn M., additional, Peterson, Eric, additional, Schultz-Darken, Nancy, additional, O’Connor, David H., additional, Mohr, Emma L., additional, Golos, Thaddeus G., additional, Aliota, Matthew T., additional, and Friedrich, Thomas C., additional

Published
2020
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8. Quantitative definition of neurobehavior, vision, hearing and brain volumes in macaques congenitally exposed to Zika virus

Author

Koenig, Michelle R., primary, Razo, Elaina, additional, Mitzey, Ann, additional, Newman, Christina M., additional, Dudley, Dawn M., additional, Breitbach, Meghan E., additional, Semler, Matthew R., additional, Stewart, Laurel M., additional, Weiler, Andrea M., additional, Rybarczyk, Sierra, additional, Bach, Kathryn M., additional, Mohns, Mariel S., additional, Simmons, Heather A., additional, Mejia, Andres, additional, Fritsch, Michael, additional, Dennis, Maria, additional, Teixeira, Leandro B. C., additional, Schotzko, Michele L., additional, Nork, T. Michael, additional, Rasmussen, Carol A., additional, Katz, Alex, additional, Nair, Veena, additional, Hou, Jiancheng, additional, Hartman, Amy, additional, Ver Hoeve, James, additional, Kim, Charlene, additional, Schneider, Mary L., additional, Ausderau, Karla, additional, Kohn, Sarah, additional, Jaeger, Anna S., additional, Aliota, Matthew T., additional, Hayes, Jennifer M., additional, Schultz-Darken, Nancy, additional, Eickhoff, Jens, additional, Antony, Kathleen M., additional, Noguchi, Kevin, additional, Zeng, Xiankun, additional, Permar, Sallie, additional, Prabhakaran, Vivek, additional, Capuano, Saverio, additional, Friedrich, Thomas C., additional, Golos, Thaddeus G., additional, O’Connor, David H., additional, and Mohr, Emma L., additional

Published
2020
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9. Pharyngeal motor cortex grey matter abnormalities and retinal photoreceptor layer dysfunction in macaques exposed to Zika virus in utero

Author

Koenig, Michelle R., Razo, Elaina, Mitzey, Ann, Semler, Matthew R., Stewart, Laurel M., Breitbach, Meghan E., Newman, Christina M., Dudley, Dawn M., Weiler, Andrea M., Rybarczyk, Sierra, Bach, Kathryn M., Mohns, Mariel S., Simmons, Heather A., Mejia, Andres, Dennis, Maria, Teixeira, Leandro B. C., Schotzko, Michele L., Nork, T. Michael, Rasmussen, Carol A., Katz, Alex, Hou, Jiancheng, Hartman, Amy, Ver Hoeve, James, Kim, Charlene, Schneider, Mary L., Ausderau, Karla, Kohn, Sarah, Jaeger, Anna S., Aliota, Matthew T., Salamat, M. Shahriar, Hayes, Jennifer M., Schultz-Darken, Nancy, Eickhoff, Jens, Antony, Kathleen M., Noguchi, Kevin, Zeng, Xiankun, Permar, Sallie, Ikonomidou, Chrysanthy, Prabhakaran, Vivek, Capuano III, Saverio, Friedrich, Thomas C., Golos, Thaddeus G., O’Connor, David H., and Mohr, Emma L.

Abstract

One third of infants who have prenatal Zika virus (ZIKV) exposure and lack significant defects consistent with congenital Zika syndrome (CZS) manifest neurodevelopmental deficits in their second year of life. We hypothesized that prenatal ZIKV exposure would lead to brain abnormalities and neurodevelopmental delays in infant macaques, as measured by quantitative hearing, neurodevelopmental, ocular and brain imaging studies. We inoculated 5 pregnant rhesus macaques with ZIKV during the first trimester, monitored pregnancies with serial ultrasounds, determined plasma viral RNA (vRNA) loads, and evaluated the infants for birth defects and neurodevelopmental deficits during their first week of life. ZIKV-exposed and control infants (n=16) were evaluated with neurobehavioral assessments, ophthalmic examinations, optical coherence tomography, electroretinography with visual evoked potentials, hearing examinations, magnetic resonance imaging (MRI) of the brain, gross post mortem examination, and histopathological and vRNA analyses of approximately 40 tissues and fluids. All 5 dams had ZIKV vRNA in plasma and seroconverted following ZIKV inoculation. One pregnancy resulted in a stillbirth. The ZIKV-exposed infants had decreased cumulative feeding volumes and weight gains compared with control infants, and also had grey matter abnormalities in the pharyngeal motor cortex identified by quantitative voxel-based morphometric comparisons. Quantitative ocular studies identified differences between ZIKV-exposed and control infants in retinal layer thicknesses and electroretinograms that were not identified in qualitative ophthalmic evaluations. Despite these findings of neuropathology, no ZIKV vRNA or IgM was detected in the infants. This suggests that ZIKV exposure without measurable vertical transmission can affect brain development in utero and that subtle neurodevelopmental delays may be detected with quantitative analyses in early infancy. Quantitative brain analyses, such as these, may predict neurodevelopmental delays that manifest later in childhood and allow early intervention and targeted therapies to improve functional outcomes of ZIKV exposed children. Author Summary Human infants with born to women with Zika virus infection during pregnancy are at risk for neurodevelopmental deficits later in childhood. We hypothesized that we could identify brain abnormalities associated with neurodevelopmental deficits in infant macaques exposed to Zika virus during pregnancy. We identified brain and retinal abnormalities in Zika virus-exposed infant macaques during their first week of life, which may be related to their findings of decreased feeding and slower weight gain. None of the infants had direct evidence of Zika virus infection in their tissues, body fluids or by detection of IgM antibodies. This suggests that Zika virus exposure during pregnancy can affect brain development in utero and that quantitative brain imaging analyses may predict neurodevelopmental delays. Early identification of Zika virus-exposed children at risk of neurodevelopmental deficits would promote targeted therapies in this population and improve the functional outcome of all Zika virus exposed children.

Published
2019
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11. 692. In Vitro Antibacterial Activity of Cefiderocol Against a Multi-national Collection of Carbapenem-Nonsusceptible Gram-Negative Bacteria From Respiratory Infections: SIDERO-WT-2014–2017

Author

Rao, Sonia N, primary, Nguyen, Sean T, additional, Soriano, Melinda M, additional, Hayes, Jennifer M, additional, Hackel, Meredith M, additional, Sahm, Daniel F, additional, Tillotson, Glenn S, additional, Echols, Roger, additional, Tsuji, Masakatsu, additional, and Yamano, Yoshinori, additional

Published
2019
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12. Quantitative definition of neurobehavior, vision, hearing and brain volumes in macaques congenitally exposed to Zika virus

Author

Koenig, Michelle R., primary, Razo, Elaina, additional, Mitzey, Ann, additional, Newman, Christina M., additional, Dudley, Dawn M., additional, Breitbach, Meghan E., additional, Semler, Matthew R., additional, Stewart, Laurel M., additional, Weiler, Andrea M., additional, Rybarczyk, Sierra, additional, Bach, Kathryn M., additional, Mohns, Mariel S., additional, Simmons, Heather A., additional, Mejia, Andres, additional, Fritsch, Michael, additional, Dennis, Maria, additional, Teixeira, Leandro B. C., additional, Schotzko, Michele L., additional, Nork, T. Michael, additional, Rasmussen, Carol A., additional, Katz, Alex, additional, Nair, Veena, additional, Hou, Jiancheng, additional, Hartman, Amy, additional, Hoeve, James Ver, additional, Kim, Charlene, additional, Schneider, Mary L., additional, Ausderau, Karla, additional, Kohn, Sarah, additional, Jaeger, Anna S., additional, Aliota, Matthew T., additional, Hayes, Jennifer M., additional, Schultz-Darken, Nancy, additional, Eickhoff, Jens, additional, Antony, Kathleen M., additional, Noguchi, Kevin, additional, Zeng, Xiankun, additional, Permar, Sallie, additional, Prabhakaran, Vivek, additional, Capuano, Saverio, additional, Friedrich, Thomas C., additional, Golos, Thaddeus G., additional, O’Connor, David H., additional, and Mohr, Emma L., additional

Published
2019
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14. Molecularly barcoded Zika virus libraries to probe in vivo evolutionary dynamics

Author

Aliota, Matthew T., primary, Dudley, Dawn M., additional, Newman, Christina M., additional, Weger-Lucarelli, James, additional, Stewart, Laurel M., additional, Koenig, Michelle R., additional, Breitbach, Meghan E., additional, Weiler, Andrea M., additional, Semler, Matthew R., additional, Barry, Gabrielle L., additional, Zarbock, Katie R., additional, Haj, Amelia K., additional, Moriarty, Ryan V., additional, Mohns, Mariel S., additional, Mohr, Emma L., additional, Venturi, Vanessa, additional, Schultz-Darken, Nancy, additional, Peterson, Eric, additional, Newton, Wendy, additional, Schotzko, Michele L., additional, Simmons, Heather A., additional, Mejia, Andres, additional, Hayes, Jennifer M., additional, Capuano, Saverio, additional, Davenport, Miles P., additional, Friedrich, Thomas C., additional, Ebel, Gregory D., additional, O’Connor, Shelby L., additional, and O’Connor, David H., additional

Published
2018
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15. Ocular and uteroplacental pathology in a macaque pregnancy with congenital Zika virus infection

Author

Mohr, Emma L., primary, Block, Lindsey N., additional, Newman, Christina M., additional, Stewart, Laurel M., additional, Koenig, Michelle, additional, Semler, Matthew, additional, Breitbach, Meghan E., additional, Teixeira, Leandro B. C., additional, Zeng, Xiankun, additional, Weiler, Andrea M., additional, Barry, Gabrielle L., additional, Thoong, Troy H., additional, Wiepz, Gregory J., additional, Dudley, Dawn M., additional, Simmons, Heather A., additional, Mejia, Andres, additional, Morgan, Terry K., additional, Salamat, M. Shahriar, additional, Kohn, Sarah, additional, Antony, Kathleen M., additional, Aliota, Matthew T., additional, Mohns, Mariel S., additional, Hayes, Jennifer M., additional, Schultz-Darken, Nancy, additional, Schotzko, Michele L., additional, Peterson, Eric, additional, Capuano, Saverio, additional, Osorio, Jorge E., additional, O’Connor, Shelby L., additional, Friedrich, Thomas C., additional, O’Connor, David H., additional, and Golos, Thaddeus G., additional

Published
2018
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16. Molecularly barcoded Zika virus libraries to probein vivoevolutionary dynamics

Author

Aliota, Matthew T., primary, Dudley, Dawn M., additional, Newman, Christina M., additional, Weger-Lucarelli, James, additional, Stewart, Laurel M., additional, Koenig, Michelle R., additional, Breitbach, Meghan E., additional, Weiler, Andrea M., additional, Semler, Matthew R., additional, Barry, Gabrielle L., additional, Zarbock, Katie R., additional, Mohns, Mariel S., additional, Mohr, Emma L., additional, Venturi, Vanessa, additional, Schultz-Darken, Nancy, additional, Peterson, Eric, additional, Newton, Wendy, additional, Schotzko, Michele L., additional, Simmons, Heather A., additional, Mejia, Andres, additional, Hayes, Jennifer M., additional, Capuano, Saverio, additional, Davenport, Miles P., additional, Friedrich, Thomas C., additional, Ebel, Gregory D., additional, O’Connor, Shelby L., additional, and O’Connor, David H., additional

Published
2017
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17. Ocular and uteroplacental pathology in macaque congenital Zika virus infection

Author

Mohr, Emma L., primary, Block, Lindsey N., additional, Newman, Christina M., additional, Stewart, Laurel M., additional, Koenig, Michelle, additional, Semler, Matthew, additional, Breitbach, Meghan E., additional, Teixeira, Leandro B.C., additional, Zeng, Xiankun, additional, Weiler, Andrea M., additional, Barry, Gabrielle L., additional, Thoong, Troy H., additional, Wiepz, Gregory J., additional, Dudley, Dawn M., additional, Simmons, Heather A., additional, Mejia, Andres, additional, Morgan, Terry K., additional, Shahriar Salamat, M., additional, Kohn, Sarah, additional, Antony, Kathleen M., additional, Aliota, Matthew T., additional, Mohns, Mariel S., additional, Hayes, Jennifer M., additional, Schultz-Darken, Nancy, additional, Schotzko, Michele L., additional, Peterson, Eric, additional, Capuano, Saverio, additional, Osorio, Jorge E., additional, O’Connor, Shelby L., additional, Friedrich, Thomas C., additional, O’Connor, David H., additional, and Golos, Thaddeus G., additional

Published
2017
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18. Highly Efficient Maternal-Fetal Zika Virus Transmission in Pregnant Rhesus Macaques

Author

Nguyen, Sydney M., primary, Antony, Kathleen M., additional, Dudley, Dawn M., additional, Kohn, Sarah, additional, Simmons, Heather A., additional, Wolfe, Bryce, additional, Shahriar Salamat, M., additional, Teixeira, Leandro B. C., additional, Wiepz, Gregory J., additional, Thoong, Troy H., additional, Aliota, Matthew T., additional, Weiler, Andrea M., additional, Barry, Gabrielle L., additional, Weisgrau, Kim L., additional, Vosler, Logan J., additional, Mohns, Mariel S., additional, Breitbach, Meghan E., additional, Stewart, Laurel M., additional, Rasheed, Mustafa N., additional, Newman, Christina M., additional, Graham, Michael E., additional, Wieben, Oliver E., additional, Turski, Patrick A., additional, Johnson, Kevin M., additional, Post, Jennifer, additional, Hayes, Jennifer M., additional, Schultz-Darken, Nancy, additional, Schotzko, Michele L., additional, Eudailey, Josh A., additional, Permar, Sallie R., additional, Rakasz, Eva G., additional, Mohr, Emma L., additional, Capuano, Saverio, additional, Tarantal, Alice F., additional, Osorio, Jorge E., additional, O’Connor, Shelby L., additional, Friedrich, Thomas C., additional, O’Connor, David H., additional, and Golos, Thaddeus G., additional

Published
2017
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20. Neutrophil progenitor populations of rhesus macaques.

Author

Weisgrau, Kim L., Vosler, Logan J., Pomplun, Nicholas L., Hayes, Jennifer M., Simmons, Heather A., Friedrichs, Kristen R., and Rakasz, Eva G.

Subjects
NEUTROPHILS, RHESUS monkeys, LACTOFERRIN, MYELOPEROXIDASE, LEUCOCYTES, FLOW cytometry, ANIMAL models in research
Abstract

Captive‐bred rhesus macaques of Indian origin represent one of the most important large animal models for infectious disease, solid organ transplantation, and stem cell research. There is a dearth of information defining hematopoietic development, including neutrophil leukocyte differentiation in this species using multicolor flow cytometry. In the current study, we sought to identify cell surface markers that delineate neutrophil progenitor populations with characteristic immunophenotypes. We defined four different postmitotic populations based on their CD11b and CD87 expression pattern, and further refined their immunophenotypes using CD32, CD64, lactoferrin, and myeloperoxidase as antigenic markers. The four subsets contained myelocyte, metamyelocyte, band, and segmented neutrophil populations. We compared our flow cytometry‐based classification with the classical nuclear morphology‐based classification. We found overlap of immunological phenotype between populations of different nuclear morphology and identified phenotypically different subsets within populations of similar nuclear morphology. We assessed the responsiveness of these populations to stimulatory signals, such as LPS, fMLP, or PMA, and demonstrated significant differences between human and rhesus macaque neutrophil progenitors. In this study, we provided evidence for species‐specific features of granulopoiesis that ultimately manifested in the divergent immunophenotypes of the fully differentiated segmented neutrophils of humans and rhesus macaques. Additionally, we found functional markers that can be used to accurately quantify neutrophil progenitors by flow cytometry. Although these markers do not coincide with the classical nuclear‐morphology‐based grading, they enable us to perform functional studies monitoring immunophenotypic markers. A flow cytometric protocol using species‐specific characteristics to define rhesus macaque neutrophil progenitors in the bone marrow. [ABSTRACT FROM AUTHOR]

Published
2019
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21. Laparoscopic anti-reflux surgery for idiopathic pulmonary fibrosis at a single centre

Author

Raghu, Ganesh, primary, Morrow, Ellen, additional, Collins, Bridget F., additional, Ho, Lawrence A.T., additional, Hinojosa, Marcelo W., additional, Hayes, Jennifer M., additional, Spada, Carolyn A., additional, Oelschlager, Brant, additional, Li, Chenxiang, additional, Yow, Eric, additional, Anstrom, Kevin J., additional, Mart, Dylan, additional, Xiao, Keliang, additional, and Pellegrini, Carlos A., additional

Published
2016
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22. A rhesus macaque model of Asian-lineage Zika virus infection

Author

Dudley, Dawn M., primary, Aliota, Matthew T., additional, Mohr, Emma L., additional, Weiler, Andrea M., additional, Lehrer-Brey, Gabrielle, additional, Weisgrau, Kim L., additional, Mohns, Mariel S., additional, Breitbach, Meghan E., additional, Rasheed, Mustafa N., additional, Newman, Christina M., additional, Gellerup, Dane D., additional, Moncla, Louise H., additional, Post, Jennifer, additional, Schultz-Darken, Nancy, additional, Schotzko, Michele L., additional, Hayes, Jennifer M., additional, Eudailey, Josh A., additional, Moody, M. Anthony, additional, Permar, Sallie R., additional, O’Connor, Shelby L., additional, Rakasz, Eva G., additional, Simmons, Heather A., additional, Capuano, Saverio, additional, Golos, Thaddeus G., additional, Osorio, Jorge E., additional, Friedrich, Thomas C., additional, and O’Connor, David H., additional

Published
2016
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24. Human Stem Cell-Derived Cardiomyocytes Integrate Into the Heart of Monkeys With Right Ventricular Pressure Overload.

Author

Scholz J, Secreto FJ, Wobig J, Kurian J, Hagen C, Zinnen A, Vu D, Johnson SJ, Cetta F, Qureshi Y, Reams R, Cannon B, Heyer CM, Chang M, Fadra N, Coonen J, Simmons HA, Mejia A, Hayes JM, Basu P, Capuano S, Bondarenko V, Metzger JM, Nelson TJ, and Emborg ME

Subjects
Animals, Humans, Male, Myocardium pathology, Myocardium metabolism, Myocardium cytology, Cell Differentiation, Disease Models, Animal, Myocytes, Cardiac cytology, Myocytes, Cardiac metabolism, Macaca mulatta, Induced Pluripotent Stem Cells cytology, Induced Pluripotent Stem Cells metabolism
Abstract

Cardiac ventricular pressure overload affects patients with congenital heart defects and can cause cardiac insufficiency. Grafts of stem cell-derived cardiomyocytes are proposed as a complementary treatment to surgical repair of the cardiac defect, aiming to support ventricular function. Here, we report successful engraftment of human induced pluripotent stem cell-derived cardiac lineage cells into the heart of immunosuppressed rhesus macaques with a novel surgical model of right ventricular pressure overload. The human troponin+ grafts were detected in low-dose (2 × 10 6 cells/kg) and high-dose (10 × 10 6 cells/kg) treatment groups up to 12 weeks post-injection. Transplanted cells integrated and progressively matched the organization of the surrounding host myocardium. Ventricular tachycardia occurred in five out of 16 animals receiving cells, with episodes of incessant tachycardia observed in two animals; ventricular tachycardia events resolved within 19 days. Our results demonstrate that grafted cardiomyocytes mature and integrate into the myocardium of nonhuman primates modeling right ventricular pressure overload., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Published
2024
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