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Mesenchymal stem ce...
Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms
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Zhu, RJ (author)
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Yan, TD (author)
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Feng, YM (author)
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show more...
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Liu, Y (author)
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Cao, HC (author)
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Peng, GX (author)
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Yang, YL (author)
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Xu, Z (author)
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Liu, JQ (author)
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Hou, W (author)
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Wang, XY (author)
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Li, Z (author)
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Deng, LC (author)
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Wang, SH (author)
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Li, J (author)
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Han, Q (author)
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Li, HL (author)
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Shan, GL (author)
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Cao, YH (author)
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An, XY (author)
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Yan, JS (author)
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Zhang, ZH (author)
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Li, HF (author)
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Qu, XB (author)
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Zhu, JQ (author)
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Zhou, SM (author)
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Wang, J (author)
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Zhang, FC (author)
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Gao, JM (author)
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Jin, RH (author)
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Xu, DY (author)
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Ma, YQ (author)
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Huang, T (author)
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Peng, S (author)
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Zheng, Z (author)
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Stambler, I (author)
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Gilson, E (author)
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Lim, LW (author)
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Moskalev, A (author)
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Cano, A (author)
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Chakrabarti, S (author)
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- Ulfhake, B (author)
- Karolinska Institutet
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Su, HX (author)
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Xu, HY (author)
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Xu, SH (author)
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Wei, F (author)
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Brown-Borg, HM (author)
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Min, KJ (author)
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Ellison-Hughes, G (author)
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Caruso, C (author)
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Jin, KL (author)
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Zhao, RC (author)
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(creator_code:org_t)
- 2021-10-26
- 2021
- English.
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In: Cell research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 31:12, s. 1244-1262
- Related links:
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https://www.nature.c...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
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- 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.
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Zhu, RJ
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Yan, TD
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Feng, YM
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Liu, Y
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Cao, HC
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Peng, GX
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show more...
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Yang, YL
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Xu, Z
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Liu, JQ
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Hou, W
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Wang, XY
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Li, Z
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Deng, LC
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Wang, SH
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Li, J
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Han, Q
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Li, HL
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Shan, GL
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Cao, YH
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An, XY
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Yan, JS
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Zhang, ZH
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Li, HF
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Qu, XB
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Zhu, JQ
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Zhou, SM
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Wang, J
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Zhang, FC
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Gao, JM
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Jin, RH
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Xu, DY
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Ma, YQ
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Huang, T
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Peng, S
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Zheng, Z
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Stambler, I
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Gilson, E
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Lim, LW
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Moskalev, A
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Cano, A
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Chakrabarti, S
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Ulfhake, B
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Su, HX
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Xu, HY
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Xu, SH
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Wei, F
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Brown-Borg, HM
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Min, KJ
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Ellison-Hughes, ...
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Caruso, C
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Jin, KL
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Zhao, RC
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show less...
- Articles in the publication
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Cell research
- By the university
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Karolinska Institutet