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- Zhu, RJ, et al.
(författare)
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Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms
- 2021
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Ingår i: Cell research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 31:12, s. 1244-1262
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Tidskriftsartikel (refereegranskat)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.
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- Hazy, James K., et al.
(författare)
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Technology Leverage and Sustainable Society Systems : A Call for Technology Forecasting that Anticipates Innovation
- 2011
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Ingår i: International Journal of Society Systems Science. - 1756-2511. ; 3:1-2, s. 5-20
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Tidskriftsartikel (refereegranskat)abstract
- We argue that economic value to society is created by converting input resources into valued outputs though the application of technology. To support this argument, the concept of technology leverage is introduced, and it is noted that the same input resource can be converted into different output values depending upon the technology employed in the conversion process and the state of technical innovation at the time the conversion occurs. This implies that through as yet unrealised innovations, future generations may create greater value for the same amount of resource than is currently possible. This difference has significant ramifications for current day resource allocation decisions. In addition to more conventional conservation arguments, technology leverage also recognises that the future value of retaining resources, especially non-renewable ones, may be evaluated using real option valuation techniques. These concepts are helpful in determining more comprehensive policies relating to resource allocation decisions.
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