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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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4. Trans liberation under neoliberal governmentality: An argument against rights-based activism

Author

Simmons, Heather M.

Subjects
Activism, Human rights, Gay liberation movement, Gay and lesbian rights, Hate crimes, Political issue, Psychology and mental health
Abstract

During the 1980s, the increasing institutionalization of the North American gay and lesbian rights movement drastically shifted the goals and methods of 2SLGBTQIA+ activism. Organizations began to focus on achieving [...]

Published
2023
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6. Sequestration and Destruction of Rinderpest Virus--Containing Material 10 Years after Eradication

Author

Budke, Christine M., Pfeiffer, Dirk U., Jones, Bryony A., Fournie, Guillaume, Kim, Younjung, Marrana, Mariana, and Simmons, Heather L.

Subjects
Epidemics -- Control -- United States, Hazardous substances -- Waste management, Medical wastes -- Waste management, Rinderpest -- Control, Health
Abstract

In 2011, ten years after the last confirmed outbreak, the Food and Agriculture Organization of the United Nations (FAO) and the World Organisation for Animal Health (WOAH, formerly OIE) jointly [...]

Published
2022
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7. Combined Treatment of Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes and Endothelial Cells Regenerate the Infarcted Heart in Mice and Non-Human Primates

Author

Cheng, Yu-Che, Hsieh, Marvin L., Lin, Chen-Ju, Chang, Cindy M.C., Huang, Ching-Ying, Puntney, Riley, Wu Moy, Amy, Ting, Chien-Yu, Herr Chan, Darien Zhing, Nicholson, Martin W., Lin, Po-Ju, Chen, Hung-Chih, Kim, Gina C., Zhang, Jianhua, Coonen, Jennifer, Basu, Puja, Simmons, Heather A., Liu, Yen-Wen, Hacker, Timothy A., Kamp, Timothy J., and Hsieh, Patrick C.H.

Published
2023
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8. Efficient in vivo neuronal genome editing in the mouse brain using nanocapsules containing CRISPR-Cas9 ribonucleoproteins

Author

Metzger, Jeanette M., Wang, Yuyuan, Neuman, Samuel S., Snow, Kathy J., Murray, Stephen A., Lutz, Cathleen M., Bondarenko, Viktoriya, Felton, Jesi, Gimse, Kirstan, Xie, Ruosen, Li, Dongdong, Zhao, Yi, Flowers, Matthew T., Simmons, Heather A., Roy, Subhojit, Saha, Krishanu, Levine, Jon E., Emborg, Marina E., and Gong, Shaoqin

Published
2023
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10. Metabolism in the Midwest: research from the Midwest Aging Consortium at the 49th Annual Meeting of the American Aging Association

Author

Murphy, Michaela E., Narasimhan, Akilavalli, Adrian, Alexis, Kumar, Ankur, Green, Cara L., Soto-Palma, Carolina, Henpita, Chathurika, Camell, Christina, Morrow, Christopher S., Yeh, Chung-Yang, Richardson, Claire E., Hill, Cristal M., Moore, Darcie L., Lamming, Dudley W., McGregor, Eric R., Simmons, Heather A., Pak, Heidi H., Bai, Hua, Denu, John M., Clark, Josef, Simcox, Judith, Chittimalli, Kishore, Dahlquist, Korbyn, Lee, Kyoo-a, Calubag, Mariah, Bouska, Mark, Yousefzadeh, Matthew J., Sonsalla, Michelle, Babygirija, Reji, Yuan, Rong, Tsuji, Tadataka, Rhoads, Timothy, Menon, Vinal, Jarajapu, Yagna PR., and Zhu, Yun

Published
2022
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12. Cotyledon‐Specific Flow Evaluation of Rhesus Macaque Placental Injury Using Ferumoxytol Dynamic Contrast‐Enhanced MRI

Author

Chen, Ruiming, primary, Seiter, Daniel, additional, Keding, Logan T., additional, Vazquez, Jessica, additional, Antony, Kathleen M., additional, Simmons, Heather A., additional, Basu, Puja, additional, Mejia, Andres F., additional, Johnson, Kevin M., additional, Stanic, Aleksandar K., additional, Liu, Ruo‐Yu, additional, Shah, Dinesh M., additional, Golos, Thaddeus G., additional, and Wieben, Oliver, additional

Published
2024
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14. Developing One Health capacity and networks through virtual training

Author

Arevalo, Maria de la Puente, primary, Maud, Jenny, additional, Alviti, Alessandra, additional, Tang, Hao, additional, George, Acty, additional, Simmons, Heather, additional, Castellan, David, additional, Siriaroonrat, Boripat, additional, Neill, Eimear O, additional, Longchar, Achila, additional, Nova, Rodrigo J., additional, Chikurunhe, Wilmot, additional, Obonyo, Mark, additional, Newman, Scott, additional, Dhingra, Madhur, additional, and Sumption, Keith, additional

Published
2023
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16. Nanoparticle-mediated delivery of insulin-like growth factor 1 to the placenta in the non-human primate is safe and regulates placental signaling

Author

Wilson, Rebecca L., primary, Schmidt, Jenna Kropp, additional, Ren, Emily, additional, Keding, Logan T., additional, Shaw, Sarah A., additional, Heselton, Avery R., additional, Schotzko, Michele L., additional, Antony, Kathleen M., additional, Fitz, Casey, additional, Simmons, Heather A., additional, Basu, Puja, additional, Golos, Thaddeus G., additional, and Jones, Helen N., additional

Published
2023
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18. Vertical transmission of African-lineage Zika virus through the fetal membranes in a rhesus macaque (Macaca mulatta) model

Author

Koenig, Michelle R., primary, Mitzey, Ann M., additional, Zeng, Xiankun, additional, Reyes, Leticia, additional, Simmons, Heather A., additional, Morgan, Terry K., additional, Bohm, Ellie K., additional, Pritchard, Julia C., additional, Schmidt, Jenna A., additional, Ren, Emily, additional, Leyva Jaimes, Fernanda B., additional, Winston, Eva, additional, Basu, Puja, additional, Weiler, Andrea M., additional, Friedrich, Thomas C., additional, Aliota, Matthew T., additional, Mohr, Emma L., additional, and Golos, Thaddeus G., additional

Published
2023
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20. Infection of the maternal-fetal interface and vertical transmission following low-dose inoculation of pregnant rhesus macaques (Macaca mulatta) with an African-lineage Zika virus

Author

Koenig, Michelle R., primary, Mitzey, Ann M., additional, Morgan, Terry K., additional, Zeng, Xiankun, additional, Simmons, Heather A., additional, Mejia, Andres, additional, Leyva Jaimes, Fernanda, additional, Keding, Logan T., additional, Crooks, Chelsea M., additional, Weiler, Andrea M., additional, Bohm, Ellie K., additional, Aliota, Matthew T., additional, Friedrich, Thomas C., additional, Mohr, Emma L., additional, and Golos, Thaddeus G., additional

Published
2023
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21. Fetal Tissues Reflect Decidual-Placental Inflammation

Author

Vazquez, Jessica, primary, Keding, Logan, additional, Koenig, Michelle R, additional, Schotzko, Michele, additional, Antony, Kathleen, additional, Racine, Jenna, additional, Simmons, Heather A, additional, Shah, Dinesh M, additional, Wieben, Oliver, additional, and Golos, Thaddeus, additional

Published
2023
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22. Frequent first-trimester pregnancy loss in rhesus macaques infected with African-lineage Zika virus

Author

Rosinski, Jenna R., primary, Raasch, Lauren E., additional, Barros Tiburcio, Patrick, additional, Breitbach, Meghan E., additional, Shepherd, Phoenix M., additional, Yamamoto, Keisuke, additional, Razo, Elaina, additional, Krabbe, Nicholas P., additional, Bliss, Mason I., additional, Richardson, Alexander D., additional, Einwalter, Morgan A., additional, Weiler, Andrea M., additional, Sneed, Emily L., additional, Fuchs, Kerri B., additional, Zeng, Xiankun, additional, Noguchi, Kevin K., additional, Morgan, Terry K., additional, Alberts, Alexandra J., additional, Antony, Kathleen M., additional, Kabakov, Sabrina, additional, Ausderau, Karla K., additional, Bohm, Ellie K., additional, Pritchard, Julia C., additional, Spanton, Rachel V., additional, Ver Hoove, James N., additional, Kim, Charlene B. Y., additional, Nork, T. Michael, additional, Katz, Alex W., additional, Rasmussen, Carol A., additional, Hartman, Amy, additional, Mejia, Andres, additional, Basu, Puja, additional, Simmons, Heather A., additional, Eickhoff, Jens C., additional, Friedrich, Thomas C., additional, Aliota, Matthew T., additional, Mohr, Emma L., additional, Dudley, Dawn M., additional, O’Connor, David H., additional, and Newman, Christina M., additional

Published
2023
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23. Combined Treatment of Human Induced Pluripotent Stem Cell--Derived Cardiomyocytes and Endothelial Cells Regenerate the Infarcted Heart in Mice and Non-Human Primates.

Author

Yu-Che Cheng, Hsieh, Marvin L., Chen-Ju Lin, Chang, Cindy M. C., Ching-Ying Huang, Puntney, Riley, Wu Moy, Amy, Chien-Yu Ting, Zhing Herr Chan, Darien, Nicholson, Martin W., Po-Ju Lin, Hung-Chih Chen, Kim, Gina C., Jianhua Zhang, Coonen, Jennifer, Puja Basu, Simmons, Heather A., Yen-Wen Liu, Hacker, Timothy A., and Kamp, Timothy J.

Published
2023
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25. Frequent first-trimester pregnancy loss in rhesus macaques infected with African-lineage Zika virus

Author

Rosinski, Jenna R., primary, Raasch, Lauren E., additional, Tiburcio, Patrick Barros, additional, Breitbach, Meghan E., additional, Shepherd, Phoenix M., additional, Yamamoto, Keisuke, additional, Razo, Elaina, additional, Krabbe, Nicholas P., additional, Bliss, Mason I., additional, Richardson, Alexander D., additional, Einwalter, Morgan A., additional, Weiler, Andrea M., additional, Sneed, Emily L., additional, Fuchs, Kerri B., additional, Zeng, Xiankun, additional, Noguchi, Kevin K., additional, Morgan, Terry K., additional, Alberts, Alexandra J., additional, Antony, Kathleen M., additional, Kabakov, Sabrina, additional, Ausderau, Karla K., additional, Bohm, Ellie K., additional, Pritchard, Julia C., additional, Spanton, Rachel V., additional, Ver Hoove, James N., additional, Kim, Charlene B. Y., additional, Nork, T. Michael, additional, Katz, Alex W., additional, Rasmussen, Carol A., additional, Hartman, Amy, additional, Mejia, Andres, additional, Basu, Puja, additional, Simmons, Heather A., additional, Eickhoff, Jens C., additional, Friedrich, Thomas C., additional, Aliota, Matthew T., additional, Mohr, Emma L., additional, Dudley, Dawn M., additional, O’Connor, David H., additional, and Newman, Christina M., additional

Published
2022
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29. Assessment of safety and immunogenicity of MHC homozygous iPSC-derived CD34+ hematopoietic progenitors in an NHP model

Author

D’Souza, Saritha S., primary, Kumar, Akhilesh, additional, Maufort, John, additional, Weinfurter, Jason T., additional, Raymond, Matthew, additional, Strelchenko, Nick S., additional, Perrin, Elizabeth, additional, Coonen, Jennifer, additional, Mejia, Andres, additional, Simmons, Heather A., additional, Torbett, Bruce E., additional, Reynolds, Matthew, additional, Thomson, James A., additional, and Slukvin, Igor I., additional

Published
2022
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31. Sarcinasp. as a presumptive cause of fatal acute gastric dilation and gastric emphysema in rhesus macaques

Author

Lee, Laura M., Owens, Leah A., Krugner-Higby, Lisa A., Graham, Melissa, Simmons, Heather A., Climans, Megan, Brown, Kelsey, Bennett, Allyson J., Schaefer, Jennifer, Meyer, Kyle, and Goldberg, Tony L.

Abstract

A 4-y-old female and 3-y-old male rhesus macaque (Macaca mulatta), both housed in the same facility, died unexpectedly within 2 wk. Postmortem examination revealed severe gastric dilation in both macaques and gastric emphysema in the female macaque. Histologically, bacteria consistent with Sarcinasp. were present in both macaques within the lungs and lumen of the trachea, esophagus, and gastrointestinal (GI) tract without associated inflammation. Additionally, in the female macaque, the bacteria were found in the gastric mucosa and associated with emphysematous spaces in the gastric wall without associated inflammation. PCR and Sanger sequencing of amplicons were subsequently performed on GI contents and non-alimentary tissues from the 2 affected monkeys and on comparative samples from unaffected rhesus monkeys in the same facility and an adjacent primate facility. The cases were compared using the 2-tailed Fisher exact test (p-value at 95% confidence). PCR identified Sarcinain GI contents of both affected and unaffected monkeys (p= 0.6084) and in non-alimentary tissues of affected monkeys only (p= 0.0083). These results suggest that the presence of Sarcinasp. in non-alimentary tissues is associated with gastric distension, gas accumulation, and unexpected death in nonhuman primates.

Published
2023
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32. Listeria monocytogenesinfection in pregnant macaques alters the maternal gut microbiome†

Author

Hugon, Anna Marie, Deblois, Courtney L, Simmons, Heather A, Mejia, Andres, Schotzo, Michele L, Czuprynski, Charles J, Suen, Garret, and Golos, Thaddeus G

Abstract

Intestinal microbial composition in macaques is influenced by interaction between the pregnant state and exposure to Listeria monocytogenes, associated in particular with significant changes to Akkermansia, Eubacterium ruminantium, Methanobrevibacter, Prevotella, and Treponema.Graphical Abstract

Published
2023
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33. Fetal loss in pregnant rhesus macaques infected with high-dose African-lineage Zika virus

Author

Raasch, Lauren E., primary, Yamamoto, Keisuke, additional, Newman, Christina M., additional, Rosinski, Jenna R., additional, Shepherd, Phoenix M., additional, Razo, Elaina, additional, Crooks, Chelsea M., additional, Bliss, Mason I., additional, Breitbach, Meghan E., additional, Sneed, Emily L., additional, Weiler, Andrea M., additional, Zeng, Xiankun, additional, Noguchi, Kevin K., additional, Morgan, Terry K., additional, Fuhler, Nicole A., additional, Bohm, Ellie K., additional, Alberts, Alexandra J., additional, Havlicek, Samantha J., additional, Kabakov, Sabrina, additional, Mitzey, Ann M., additional, Antony, Kathleen M., additional, Ausderau, Karla K., additional, Mejia, Andres, additional, Basu, Puja, additional, Simmons, Heather A., additional, Eickhoff, Jens C., additional, Aliota, Matthew T., additional, Mohr, Emma L., additional, Friedrich, Thomas C., additional, Golos, Thaddeus G., additional, O’Connor, David H., additional, and Dudley, Dawn M., additional

Published
2022
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34. Efficient in vivo neuronal genome editing in the mouse brain using nanocapsules containing CRISPR-Cas9 ribonucleoproteins

Author

Metzger, Jeanette M., primary, Wang, Yuyuan, additional, Neuman, Samuel S., additional, Snow, Kathy J., additional, Murray, Stephen A., additional, Lutz, Cathleen M., additional, Bondarenko, Viktoriya, additional, Felton, Jesi, additional, Gimse, Kirstan, additional, Xie, Ruosen, additional, Zhao, Yi, additional, Flowers, Matthew T., additional, Simmons, Heather A., additional, Roy, Subhojit, additional, Saha, Krishanu, additional, Levine, Jon, additional, Emborg, Marina E., additional, and Gong, Shaoqin, additional

Published
2022
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35. Human immune globulin treatment controls Zika viremia in pregnant rhesus macaques

Author

Dudley, Dawn M., primary, Koenig, Michelle R., additional, Stewart, Laurel M., additional, Semler, Matthew R., additional, Newman, Christina M., additional, Shepherd, Phoenix M., additional, Yamamoto, Keisuke, additional, Breitbach, Meghan E., additional, Schotzko, Michele, additional, Kohn, Sarah, additional, Antony, Kathleen M., additional, Qiu, Hongyu, additional, Tunga, Priyadarshini, additional, Anderson, Deborah M., additional, Guo, Wendi, additional, Dennis, Maria, additional, Singh, Tulika, additional, Rybarczyk, Sierra, additional, Weiler, Andrea M., additional, Razo, Elaina, additional, Mitzey, Ann, additional, Zeng, Xiankun, additional, Eickhoff, Jens C., additional, Mohr, Emma L., additional, Simmons, Heather A., additional, Fritsch, Michael K., additional, Mejia, Andres, additional, Aliota, Matthew T., additional, Friedrich, Thomas C., additional, Golos, Thaddeus G., additional, Kodihalli, Shantha, additional, Permar, Sallie R., additional, and O’Connor, David H., additional

Published
2022
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37. Infection of the maternal-fetal interface and vertical transmission following low-dose inoculation of pregnant rhesus macaques (Macaca mulatta) with an African-lineage Zika virus

Author

Koenig, Michelle R., primary, Mitzey, Ann M., additional, Morgan, Terry K., additional, Zeng, Xiankun, additional, Simmons, Heather A., additional, Mejia, Andres, additional, Jaimes, Fernanda Leyva, additional, Keding, Logan T., additional, Crooks, Chelsea M., additional, Weiler, Andrea M., additional, Bohm, Ellie K., additional, Aliota, Matthew T., additional, Friedrich, Thomas C., additional, Mohr, Emma L., additional, and Golos, Thaddeus G., additional

Published
2022
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38. Fetal loss in pregnant rhesus macaques infected with high-dose African-lineage Zika virus

Author

Raasch, Lauren, primary, Yamamoto, Keisuke, additional, Newman, Christina M, additional, Rosinski, Jenna R, additional, Shepherd, Phoenix M, additional, Razo, Elaina, additional, Crooks, Chelsea M, additional, Bliss, Mason I, additional, Breitbach, Meghan E, additional, Sneed, Emily L, additional, Weiler, Andrea M, additional, Zeng, Xiankun, additional, Noguchi, Kevin K, additional, Morgan, Terry K, additional, Fuhler, Nicole A, additional, Bohm, Ellie K, additional, Alberts, Alexandra J, additional, Havlicek, Samantha J, additional, Kabakov, Sabrina, additional, Mitzey, Ann M, additional, Antony, Kathleen M, additional, Ausderau, Karla K, additional, Mejia, Andres, additional, Basu, Puja, additional, Simmons, Heather A, additional, Eickhoff, Jens C, additional, Aliota, Matthew T, additional, Mohr, Emma L, additional, Friedrich, Thomas C, additional, Golos, Thaddeus G, additional, O'Connor, David H, additional, and Dudley, Dawn M, additional

Published
2022
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40. AgSecure Africa ProgrammeTM: A Blended Training Approach for Africa

Author

Arenas-Gamboa, Angela M., primary, Simmons, Heather L., additional, Krecek, Rosina C., additional, Logan, Linda L., additional, Ellis, Dee, additional, Ptaschinski, Maryn, additional, Cargill, Jessica S., additional, Werre, Stephen R., additional, Mulumba, Misheck, additional, and Heath, Livio, additional

Published
2021
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44. Assessment of safety and immunogenicity of MHC homozygous iPSC-derived CD34+hematopoietic progenitors in an NHP model

Author

D'Souza, Saritha S., Kumar, Akhilesh, Maufort, John, Weinfurter, Jason T., Raymond, Matthew, Strelchenko, Nick S., Perrin, Elizabeth, Coonen, Jennifer, Mejia, Andres, Simmons, Heather A., Torbett, Bruce E., Reynolds, Matthew, Thomson, James A., and Slukvin, Igor I.

Abstract

Administration of ex vivo expanded somatic myeloid progenitors has been explored as a way to facilitate a more rapid myeloid recovery and improve overall survival after myeloablation. Recent advances in induced pluripotent stem cell (iPSC) technologies have created alternative platforms for supplying off-the-shelf immunologically compatible myeloid progenitors, including cellular products derived from major histocompatibility complex (MHC) homozygous superdonors, potentially increasing the availability of MHC-matching cells and maximizing the utility of stem cell banking. However, the teratogenic and tumorigenic potential of iPSC-derived progenitor cells and whether they will induce alloreactive antibodies upon transfer remain unclear. We evaluated the safety and efficacy of using CD34+CD45+hematopoietic progenitors derived from MHC homozygous iPSCs (iHPs) to treat cytopenia after myeloablative hematopoietic stem cell (HSC) transplantation in a Mauritian cynomolgus macaque (MCM) nonhuman primate (NHP) model. We demonstrated that infusion of iHPs was well tolerated and safe, observing no teratomas or tumors in the MCMs up to 1 year after HSC transplantation and iHP infusion. Importantly, the iHPs also did not induce significant levels of alloantibodies in MHC-matched or -mismatched immunocompetent MCMs, even after increasing MHC expression on iHPs with interferon-γ. These results support the feasibility of iHP use in the setting of myeloablation and suggest that iHP products pose a low risk of inducing alloreactive antibodies.

Published
2022
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45. Metabolism in the Midwest: research from the Midwest Aging Consortium at the 49th Annual Meeting of the American Aging Association.

Author

Murphy, Michaela E., Narasimhan, Akilavalli, Adrian, Alexis, Kumar, Ankur, Green, Cara L., Soto-Palma, Carolina, Henpita, Chathurika, Camell, Christina, Morrow, Christopher S., Yeh, Chung-Yang, Richardson, Claire E., Hill, Cristal M., Moore, Darcie L., Lamming, Dudley W., McGregor, Eric R., Simmons, Heather A., Pak, Heidi H., Bai, Hua, Denu, John M., and Clark, Josef

Subjects
LOW-calorie diet, INTERMEDIATE filament proteins, METABOLISM, OLDER people
Abstract

As the aging population on a global and national scale reaches ever increasing highs, research is essential to reduce the burden of aging and age-related diseases. I Vav-iCre i SP ± sp I ;Ercc1 i SP I -/fl i sp mice are healthy into adulthood, but then display premature onset of immunosenescence characterized by senescence of specific immune cell populations and impaired immune function, similar to changes that occur with aging in wild-type mice. B Dr. Claire Richardson b , University of Wisconsin-Madison, investigated how aging affects neuron cell biology by exploiting the ability of the nematode I Caenorhabditis i elegans to de-couple the symptoms of aging from chronological age [[61]]. They discovered that morphological aging is cell-intrinsically controlled by focusing on features of neuron morphological aging. LSD1 also targets non-histone proteins p53 and RelA/p65, which contribute to senescence and the secretory phenotype of senescent cells (senescence-associated secretory phenotype or SASP). [Extracted from the article]

Published
2022
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48. Preclinical evaluation of transaxial intraputaminal trajectory for enhanced distribution of grafted cells in Parkinson's disease.

Author

Emborg ME, Mancinelli A, Colwell JC, Zinnen AD, Pape B, Brunner K, Bondarenko V, Fitz C, Coonen J, Menna V, Fuchs K, Schultz-Darken N, Simmons HA, Tran H, Larson P, Olsen M, Hurley S, Bratt-Leal AM, Wirth E, and Metzger JM

Abstract

Objective: The objective of this study was to develop and evaluate the feasibility and safety of a novel transaxial surgical approach for the delivery of human induced pluripotent stem cell-derived dopaminergic neuroprogenitor cells (DANPCs) into the putamen nucleus using nonhuman primates and surgical techniques and tools relevant to human clinical translation., Methods: Nine immunosuppressed, unlesioned adult cynomolgus macaques (4 females, 5 males) received intraputaminal injections of vehicle or DANPCs (0.9 × 105 to 1.1 × 105 cells/µL) under real-time intraoperative MRI guidance. The infusates were combined with 1-mM gadoteridol (for intraoperative MRI visualization) and delivered via two tracks per hemisphere (ventral and dorsal) using a transaxial approach. The total volumes of infusion were 25 µL and 50 µL for the right and left putamen, respectively (infusion rate 2.5 µL/min). Animals were evaluated with a battery of clinical and behavioral outcome measures and euthanized 7 or 30 days postsurgery; full necropsies were performed by a board-certified veterinary pathologist. Brain tissues were collected and processed for immunohistochemistry, including against the human-specific marker STEM121., Results: The optimized surgical technique and tools produced successful targeting of the putamen via the transaxial approach. Intraoperative MR images confirmed on-target intraputaminal injections in all animals. All animals survived to scheduled termination without clinical evidence of neurological deficits. The first 4 animals to undergo surgery had mild brain swelling noted at the end of surgery, of which 3 had transient reduced vision; administration of mannitol therapy and reduced intravenous fluid during the surgical procedure addressed these complications. Immunostaining against STEM121 confirmed the presence of grafted cells along the injection track within the targeted putamen area of DANPC-treated animals. All adverse histological findings were limited in scope and consistent with surgical manipulation, injection procedure, and postsurgical inflammatory response to the mechanical disruption caused by the cannula insertion., Conclusions: The delivery system, injection procedure, and DANPCs were well tolerated in all animals. Prevention of mild brain swelling by mannitol dosing and reduction of intravenous fluids during surgery allowed visual effects to be avoided. The results of the study established that this novel transaxial approach can be used to correctly and safely target cell injections to the postcommissural putamen and support clinical investigation.

Published
2024
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49. Mpox virus (MPXV) vertical transmission and fetal demise in a pregnant rhesus macaque model.

Author

Krabbe NP, Mitzey AM, Bhattacharya S, Razo ER, Zeng X, Bekiares N, Moy A, Kamholz A, Karl JA, Daggett G, VanSleet G, Morgan T, Capuano SV, Simmons HA, Basu P, Weiler AM, O'Connor DH, Friedrich TC, Golos TG, and Mohr EL

Abstract

Infection with clade I Mpox virus (MPXV) results in adverse pregnancy outcomes, yet the potential for vertical transmission resulting in fetal harm with clade IIb MPXV, the clade that is currently circulating in the Western Hemisphere, remains unknown. We established a rhesus macaque model of vertical MPXV transmission with early gestation inoculation. Three pregnant rhesus macaques were inoculated intradermally with 1.5 × 10^5 plaque forming units (PFU) of clade IIb MPXV near gestational day (GD) 30 and animals were monitored for viremia and maternal and fetal well-being. Animals were euthanized to collect tissues at 5, 14, or 25 days post-inoculation (dpi). Tissues were evaluated for viral DNA (vDNA) loads, infectious virus titers, histopathology, MPXV mRNA and protein localization, as well as MPXV protein co-localization with placental cells including, Hofbauer cells, mesenchymal stromal cells, endothelial cells, and trophoblasts. vDNA was detected in maternal blood and skin lesions by 5 dpi. Lack of fetal heartbeat was observed at 14 or 25 dpi for two dams indicating fetal demise; the third dam developed significant vaginal bleeding at 5 dpi and was deemed an impending miscarriage. vDNA was detected in placental and fetal tissue in both fetal demise cases. MPXV localized to placental villi by ISH and IHC. Clade IIb MPXV infection in pregnant rhesus macaques results in vertical transmission to the fetus and adverse pregnancy outcomes, like clade I MPXV. Further studies are needed to determine whether antiviral therapy with tecovirimat will prevent vertical transmission and improve pregnancy outcomes., One Sentence Summary: Clade IIb Mpox virus infection of pregnant rhesus macaques results in vertical transmission from mother to fetus and adverse pregnancy outcomes.

Published
2024
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50. Nanoparticle-mediated delivery of placental gene therapy via uterine artery catheterization in a pregnant rhesus macaque.

Author

Schmidt JK, Wilson RL, Davenport BN, Hacker TA, Fitz C, Simmons HA, Schotzko ML, Golos TG, and Jones HN

Abstract

Nanoparticles offer promise as a mechanism to non-invasively deliver targeted placental therapeutics. Our previous studies utilizing intraplacental administration demonstrate efficient nanoparticle uptake into placental trophoblast cells and overexpression of human IGF1 ( hIGF1 ). Nanoparticle-mediated placental overexpression of hIGF1 in small animal models of placental insufficiency and fetal growth restriction improved nutrient transport and restored fetal growth. The objective of this pilot study was to extend these studies to the pregnant nonhuman primate and develop a method for local delivery of nanoparticles to the placenta via maternal blood flow from the uterine artery. Nanoparticles containing hIGF1 plasmid driven by the placenta-specific PLAC1 promoter were delivered to a mid-gestation pregnant rhesus macaque via a catheterization approach that is clinically used for uterine artery embolization. Maternal-fetal interface, fetal and maternal tissues were collected four days post-treatment to evaluate the efficacy of hIGF1 treatment in the placenta. The uterine artery catheterization procedure and nanoparticle treatment was well tolerated by the dam and fetus through the four-day study period following catheterization. Nanoparticles were taken up by the placenta from maternal blood as plasmid-specific hIGF1 expression was detected in multiple regions of the placenta via in situ hybridization and qPCR. The uterine artery catheterization approach enabled successful delivery of nanoparticles to maternal circulation in close proximity to the placenta with no concerns to maternal or fetal health in this short-term feasibility study. In the future, this delivery approach can be used for preclinical evaluation of the long-term safety and efficacy of nanoparticle-mediated placental therapies in a rhesus macaque model., Highlights: Novel method to deliver therapeutics to maternal-fetal interfaceDelivery of nanoparticles to the placenta via maternal catheterization.

Published
2024
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