Umbilical cord blood derived microglia-like cells to model COVID-19 exposure
Umbilical cord blood derived microglia-like cells to model COVID-19 exposure
Abstract Microglia, the resident brain immune cells, play a critical role in normal brain development, and are impacted by the intrauterine environment, including maternal immune activation and inflammatory exposures. The COVID-19 pandemic presents a potential developmental immune challenge to the fetal brain, in the setting of maternal SARS-CoV-2 infection with its attendant potential for cytokine production and, in severe cases, cytokine storming. There is currently no biomarker or model for in utero microglial priming and function that might aid in identifying the neonates and children most vulnerable to neurodevelopmental morbidity, as microglia remain inaccessible in fetal life and after birth. This study aimed to generate patient-derived microglial-like cell models unique to each neonate from reprogrammed umbilical cord blood mononuclear cells, adapting and extending a novel methodology previously validated for adult peripheral blood mononuclear cells. We demonstrate that umbilical cord blood mononuclear cells can be used to create microglial-like cell models morphologically and functionally similar to microglia observed in vivo. We illustrate the application of this approach by generating microglia from cells exposed and unexposed to maternal SARS-CoV-2 infection. Our ability to create personalized neonatal models of fetal brain immune programming enables non-invasive insights into fetal brain development and potential childhood neurodevelopmental vulnerabilities for a range of maternal exposures, including COVID-19.
Perlis Roy H.、De Guzman Rose M.、Fu Ting、Edlow Andrea G.、Thanos Jessica M.、McCrea Liam T.、Sellgren Carl M.、Horng Joy、Sheridan Steven D.
Department of Psychiatry, Harvard Medical School||Center for Genomic Medicine and Department of Psychiatry, Massachusetts General HospitalObstetrics, Gynecology, and Reproductive Biology, Harvard Medical School||Vincent Center for Reproductive Biology, Massachusetts General HospitalDepartment of Psychiatry, Harvard Medical School||Center for Genomic Medicine and Department of Psychiatry, Massachusetts General HospitalObstetrics, Gynecology, and Reproductive Biology, Harvard Medical School||Vincent Center for Reproductive Biology, Massachusetts General HospitalDepartment of Psychiatry, Harvard Medical School||Center for Genomic Medicine and Department of Psychiatry, Massachusetts General HospitalDepartment of Psychiatry, Harvard Medical School||Center for Genomic Medicine and Department of Psychiatry, Massachusetts General HospitalDepartment of Physiology and Pharmacology, Karolinska InstitutetDepartment of Psychiatry, Harvard Medical School||Center for Genomic Medicine and Department of Psychiatry, Massachusetts General HospitalDepartment of Psychiatry, Harvard Medical School||Center for Genomic Medicine and Department of Psychiatry, Massachusetts General Hospital
医学研究方法基础医学神经病学、精神病学
Perlis Roy H.,De Guzman Rose M.,Fu Ting,Edlow Andrea G.,Thanos Jessica M.,McCrea Liam T.,Sellgren Carl M.,Horng Joy,Sheridan Steven D..Umbilical cord blood derived microglia-like cells to model COVID-19 exposure[EB/OL].(2025-03-28)[2025-05-14].https://www.biorxiv.org/content/10.1101/2020.10.07.329748.点此复制
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