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| 1 | Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms显示文摘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/progenitorlike(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. | Rongjia Zhu Tingdong Yan Yingmei Feng Yan Liu Hongcui Cao Gongxin Peng Yanlei Yang Zhen Xu Jingqi Liu Wei Hou Xiaoyue Wang Zhe Li Luchan Deng Shihua Wang Jing Li Qin Han Hongling Li Guangliang Shan Yinghao Cao Xingyan An Jianshe Yan Zhonghui Zhang Huafei Li Xuebin Qu Jiaqi Zhu Shumin Zhou Jiao Wang Fengchun Zhang Jinming Gao Ronghua Jin Dayong Xu Yan-Qing Ma Tao Huang Shuang Peng Zhi Zheng Ilia Stambler Eric Gilson Lee Wei Lim Alexey Moskalev Antonio Cano Sasanka Chakrabarti Brun Ulfhake Huanxing Su Haoying Xu Sihuan Xu Feng Wei Holly MBrown-Borg Kyung-Jin Min Georgina Ellison-Hughes Calogero Caruso Kunlin Jin Robert Chunhua Zhao | 2021 | Cell Research2021，31，12： | 5 |
| 2 | Expression of GAP-43 mRNA in the adult mammalian spinal cord under normal conditions and after different types of lesions, with special reference to motoneurons显示文摘 | H. Lind? F. Piehl ?. Dagerlind V. M. K. Verge U. Arvidsson S. Cullheim M. Risling B. Ulfhake T. H?kfelt | 1992 | Experimental Brain Research1992，，2： | 1 |
| 3 | Effect of peripheral nerve injury on dorsal root ganglion neurons in the C57BL/6J mouse: marked changes both in cell numbers and neuropeptide expression显示文摘 | Shi T J Tandrup T Bergman E Xu Z Q Ulfhake B Hokfelt T | 2001 | Neuroscience2001，105，： | 1 |
| 4 | Estrogen receptor-alpha and beta immunoreactive neurons in the brainstem and spinal cord of male and female mice:relationships to monoaminergic,cholinergic,and spinal projection system显示文摘 | Vanderhorst VG Gustafsson JA Ulfhake B | | 0，，02： | 1 |
| 5 | Retrograde olabeling of primary sensory neurons with fluorescent latex microspheres:a useful tool for long term tagging of neurons 显示文摘 | Altun M Bergman E Ulfhake B | 2001 | J Neurosci Methods2001，108，1： | 1 |
| 6 | Effects of aging and axotomy on the expression of neurotrophin receptors in primary sensory neurons 显示文摘 | Bergman E Fundin BT Ulfhake B | 1999 | J Comp Neurol1999，410，： | 1 |
| 7 | Microglial activation emergence of EDl-expressing cells and clusterin upregulation in the aging rat CNS,with special reference to the spinal cord显示文摘 | Kullberg S Aldskogius H Ulfhake B | 2001 | Brain Res2001，899，12： | 1 |
| 8 | The serotoninergic bulbospinal system and brainstem-spinal cord content of serotonin-,TRH-,and substance P-like immunoreactivity in the aged rat with special reference to the spinal cord motor nucleus显示文摘 | Johnson H Ulfhake B Dagerlind A | 1993 | Synapse1993，15，1： | 1 |
| 9 | Postnatal development of cat hind limb motoneurons:In vivo morphology of dendritic growth cones and the maturation of denⅡdrite morphology显示文摘 | Ulfhake B Cullheim S | 1988 | J Comp Neurol1988，278，： | 1 |
| 10 | Sarcopenia is not due to lack of regenerativedrive in senescent skeletal muscle 显示文摘 | Edstrom E Ulfhake B | 2005 | Aging Cell2005，4，2： | 1 |
| 11 | Effect of peripheral nerve injury on dorsal root ganglion neurons in the C57BL/6J mouse: marked changes both in cell numbers and neuropeptide expression显示文摘 | Ulfhake B Hotfelt T | 2001 | Neuroscience2001，105，1： | 1 |
| 12 | Microglial activation,emergence of ED1-expressing cells and clusterin upregulation in the aging rat CNS,with special reference to the spinal cord显示文摘 | Kullberg S Aldskogius H Ulfhake B | 2001 | Brain Res2001，899，12： | 1 |
| 13 | Anatomy of dendrites in motoneurons supplying the intrinsic muscles of the foot sole in the aged cat: evidence for dendritic growth and neo-synaptoge- nesis 显示文摘 | Ramfrez V Ulfhake B | 1992 | J Comp Neurol1992，316，1： | 1 |
| 14 | Distribu tion of enkephalin and its relation to serotonin in cat and monkey spinal cord and brain stem显示文摘 | Arvidsson U Cullheim S Ulfhake B | 1992 | Synapse1992，11，： | 1 |
| 15 | Changes in behaviors of male C57BL/6J mice across adult life span and effects of dietary restriction显示文摘 | Fahlstr6m A Zeberg H Ulfhake B | 2012 | Age (Dordr)2012，34，6： | 1 |
| 16 | Peripheral nerve section induces increased levels of calcitonin gene-related peptide (CGRP)-like immunoreactivity in axotomized motoneurons显示文摘 | U. Arvidsson H. Johnson F. Piehl S. Cullheim T. H?kfelt M. Risling L. Terenius B. Ulfhake | 1990 | Experimental Brain Research1990，，1： | 1 |
| 17 | Es-trogen receptor-a and -(3 immunoreactive neurons inthe brainstem and spinal cord of male and femalemice: Relationships to monoaminergic,cholinergic,and spinal projection systems显示文摘 | Vanderhorst VG Gustafsson JA Ulfhake B | 2005 | J Comp Neurol2005，448，2： | 1 |
| 18 | Microglial activation, emergence of ED1-expressing cells and clusterin upregulation in the aging rat CNS, with special reference to the spinal cord显示文摘 | Aldskogius H Ulfhake B | 2001 | Brain Res2001，899，12： | 1 |
| 19 | Microglial activation,emergence of ED1-expressing cells and clusterin upregulation in the aging rat CNS,with special reference to the spinal cord显示文摘 | Kullberg S Aldskogius H Ulfhake B | 2001 | Brain Res2001，899，12： | 1 |
| 20 | The organization of the brainstem and spinal cord of the mouse:relationships between monoaminergie, cho- linergic, and spinal projection systems 显示文摘 | Vander I-Iorst VG Ulfhake B | 2006 | J Chem Neuroanat2006，31，1： | 1 |
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