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Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms.


ABSTRACT: The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2+ hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors - CX3CR1 and L-selectin - were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.

SUBMITTER: Zhu R 

PROVIDER: S-EPMC8546390 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms.

Zhu Rongjia R   Yan Tingdong T   Feng Yingmei Y   Liu Yan Y   Cao Hongcui H   Peng Gongxin G   Yang Yanlei Y   Xu Zhen Z   Liu Jingqi J   Hou Wei W   Wang Xiaoyue X   Li Zhe Z   Deng Luchan L   Wang Shihua S   Li Jing J   Han Qin Q   Li Hongling H   Shan Guangliang G   Cao Yinghao Y   An Xingyan X   Yan Jianshe J   Zhang Zhonghui Z   Li Huafei H   Qu Xuebin X   Zhu Jiaqi J   Zhou Shumin S   Wang Jiao J   Zhang Fengchun F   Gao Jinming J   Jin Ronghua R   Xu Dayong D   Ma Yan-Qing YQ   Huang Tao T   Peng Shuang S   Zheng Zhi Z   Stambler Ilia I   Gilson Eric E   Lim Lee Wei LW   Moskalev Alexey A   Cano Antonio A   Chakrabarti Sasanka S   Ulfhake Brun B   Su Huanxing H   Xu Haoying H   Xu Sihuan S   Wei Feng F   Brown-Borg Holly M HM   Min Kyung-Jin KJ   Ellison-Hughes Georgina G   Caruso Calogero C   Jin Kunlin K   Zhao Robert Chunhua RC  

Cell research 20211026 12


The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P   ...[more]

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