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

TitleMesenchymal stem cell treatment improves outcome of COVID- 19 patients via multiple immunomodulatory mechanisms
Authors
Issue Date2021
Citation
Cell Research, 2021 How to Cite?
AbstractThe 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.
Persistent Identifierhttp://hdl.handle.net/10722/308298
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhu, R-
dc.contributor.authorYan, T-
dc.contributor.authorFeng, Y-
dc.contributor.authorLiu, Y-
dc.contributor.authorCao, H-
dc.contributor.authorPeng, G-
dc.contributor.authorYang, Y-
dc.contributor.authorXu, Z-
dc.contributor.authorLiu, J-
dc.contributor.authorHou, W-
dc.contributor.authorWang, X-
dc.contributor.authorLi, Z-
dc.contributor.authorDeng, L-
dc.contributor.authorWang, S-
dc.contributor.authorLi, J-
dc.contributor.authorHan, Q-
dc.contributor.authorLi, H-
dc.contributor.authorShan, G-
dc.contributor.authorCao, Y-
dc.contributor.authorAn, X-
dc.contributor.authorYan, J-
dc.contributor.authorZhang, Z-
dc.contributor.authorLi, H-
dc.contributor.authorQu, X-
dc.contributor.authorZhu, J-
dc.contributor.authorZhou, S-
dc.contributor.authorWang, J-
dc.contributor.authorZhang, F-
dc.contributor.authorGao, J-
dc.contributor.authorJin, R-
dc.contributor.authorXu, D-
dc.contributor.authorMa, YQ-
dc.contributor.authorHuang, T-
dc.contributor.authorPeng, S-
dc.contributor.authorZheng, Z-
dc.contributor.authorStambler, I-
dc.contributor.authorGilson, E-
dc.contributor.authorLim, LW-
dc.contributor.authorMoskalev, A-
dc.contributor.authorCano, A-
dc.contributor.authorChakrabarti, S-
dc.contributor.authorUlfhake, B-
dc.contributor.authorSu, H-
dc.contributor.authorXu, H-
dc.contributor.authorXu, S-
dc.contributor.authorWei, F-
dc.contributor.authorBrown-Borg, HM-
dc.contributor.authorMin, KJ-
dc.contributor.authorEllison-Hughes, G-
dc.contributor.authorCaruso, C-
dc.contributor.authorJin, K-
dc.contributor.authorZhao, RC-
dc.date.accessioned2021-11-12T13:45:18Z-
dc.date.available2021-11-12T13:45:18Z-
dc.date.issued2021-
dc.identifier.citationCell Research, 2021-
dc.identifier.urihttp://hdl.handle.net/10722/308298-
dc.description.abstractThe 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.-
dc.languageeng-
dc.relation.ispartofCell Research-
dc.titleMesenchymal stem cell treatment improves outcome of COVID- 19 patients via multiple immunomodulatory mechanisms-
dc.typeArticle-
dc.identifier.emailLim, LW: limlw@hku.hk-
dc.identifier.authorityLim, LW=rp02088-
dc.identifier.doi10.1038/s41422-021-00573-y-
dc.identifier.hkuros330353-
dc.identifier.isiWOS:000711303100002-

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