Estep Benjamin K, Kuhlmann Charles J, Osuka Satoru, Suryavanshi Gajendra W, Nagaoka-Kamata Yoshiko, Samuel Ciearria N, Blucas Madison T, Jepson Chloe E, Goepfert Paul A, Kamata Masakazu
Department of Microbiology, University of Alabama at Birmingham, 845 19 Street South, Birmingham, AL 35205, USA.
Department of Neurosurgery, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
iScience. 2022 Dec 22;25(12):105544. doi: 10.1016/j.isci.2022.105544. Epub 2022 Nov 11.
Umbilical cord blood (UCB) is an irreplaceable source for hematopoietic stem progenitor cells (HSPCs). However, the effects of SARS-CoV-2 infection and COVID-19 vaccination on UCB phenotype, specifically the HSPCs therein, are currently unknown. We thus evaluated any effects of SARS-CoV-2 infection and/or COVID-19 vaccination from the mother on the fate and functionalities of HSPCs in the UCB. The numbers and frequencies of HSPCs in the UCB decreased significantly in donors with previous SARS-CoV-2 infection and more so with COVID-19 vaccination via the induction of apoptosis, likely mediated by IFN-γ-dependent pathways. Two independent hematopoiesis assays, a colony forming unit assay and a mouse humanization assay, revealed skewed hematopoiesis of HSPCs obtained from donors delivered from mothers with SARS-CoV-2 infection history. These results indicate that SARS-CoV-2 infection and COVID-19 vaccination impair the functionalities and survivability of HSPCs in the UCB, which would make unprecedented concerns on the future of HSPC-based therapies.
脐带血(UCB)是造血干祖细胞(HSPCs)的一种不可替代的来源。然而,目前尚不清楚严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染和2019冠状病毒病(COVID-19)疫苗接种对UCB表型,特别是其中的HSPCs的影响。因此,我们评估了母亲感染SARS-CoV-2和/或接种COVID-19疫苗对UCB中HSPCs的命运和功能的任何影响。在既往感染过SARS-CoV-2的供体中,UCB中HSPCs的数量和频率显著下降,而通过诱导凋亡(可能由IFN-γ依赖途径介导)接种COVID-19疫苗的供体中下降更为明显。两项独立的造血分析,即集落形成单位分析和小鼠人源化分析,揭示了从有SARS-CoV-2感染史母亲分娩的供体中获得的HSPCs造血偏向。这些结果表明,SARS-CoV-2感染和COVID-19疫苗接种会损害UCB中HSPCs的功能和生存能力,这将对基于HSPCs的治疗的未来产生前所未有的担忧。