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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 | Europe has it's own technology base to compete with ATS program in us显示文摘 | IRWIN STAMBLER | 1995 | Gas Turbine World1995，25，6： | 2 |
| 3 | Technology base is in place for next phase of ATS development program显示文摘 | IRWIN STAMBLER | 1995 | Gas Turbine World1995，25，6： | 2 |
| 4 | Atrial fibrillation in Sub-Saharan Africa:epidemiology,unmet needs,and treatment options显示文摘 | Stambler BS Ngunga LM | 2015 | Int J Gen Med2015，14，8： | 1 |
| 5 | Conversion efficacy and safety of intravenous ibutilide compared with intravenous procainamide in patients with atrial flutter or fibrillation显示文摘 | Carber-y PA Stambler B | 1998 | J Am Coll Cardiol1998，31，6： | 1 |
| 6 | Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation显示文摘 | Stambler BS Wood MA Ellenbogen KA | 1996 | Ibutilide repeat Dose Study Investigators Circulation1996，94，： | 1 |
| 7 | Antiarrhythmic action of intravenous ibutilide compared with procainamide during human atrial flutter and fibrillation: electrophysiological determinants of enhanced conversion efficacy 显示文摘 | Wood MA Ellenbogen KA | 1997 | Circulation1997，96，12： | 1 |
| 8 | Eutrophication, marine pollution and coral reefs显示文摘 | DUBINSKY Z STAMBLER N | 1996 | Global Change Biol1996，2，： | 1 |
| 9 | Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation显示文摘 | Wood MA Ellenbogen KA | 1996 | Circulation1996，94，7： | 1 |
| 10 | Antiarrhythmic ac- tions of intravenous ibutilide compared with procainamide dur ing human atrial flutter and fibrillation electrophysiological de- terminants of enhanced conversion efficacy 显示文摘 | Stambler BS Wood MA Ellenbogen KA | 1997 | Circulation1997，96，12： | 1 |
| 11 | Efficacy of intravenous ibutilide for rapid termination of atrial fibrillation and atrial flutter: a dose-response study显示文摘 | Stambler BS Wood MA | 1996 | J Am COIl Cardiol1996，28，1： | 1 |
| 12 | Conversion efficacy and safety of intravenous ibutilide compared with intravenous procainamide in patients with atrial flutter or fibrillation显示文摘 | Volgman AS Carberry PA Stambler B | 1998 | J Am Coll Cardiol1998，31，6： | 1 |
| 13 | Efficacy of intravenous ibutilide for rapid termination of atrial fibrillation and atrial flutter: A dose-response study 显示文摘 | Ellenbngen KA Stambler BS Wood MA | 1996 | J Am Coil Cardiol1996，28，1： | 1 |
| 14 | Right ventricular outflowversus apical pacing in pacemaker patientswith congestive heart fail-ure and atrial fibrillation 显示文摘 | Stambler BS Ellenbogen K Zhang X | 2003 | J Cardiovasc Electrophysiol2003，14，： | 1 |
| 15 | Electrophysiologic deteminants of pharmacologic conversion of hunasn atrial fibrillation and flutter: enhanced efficacy of ibutilide a new class Ⅲ antiarrhythnic drug显示文摘 | Wood MA Belz MK | 1993 | Circulation1993，88，： | 1 |
| 16 | Efficacy of ibutilide for termination of atrial fibrillation and flutter显示文摘 | Clemo HW Stambler BS | 1996 | Am J Cardliol1996，78，8： | 1 |
| 17 | Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation 显示文摘 | Stambler BS Wood MA Ellenbogvn KA | 1996 | Circulation1996，94，7： | 1 |
| 18 | S- welling-activated chloride current is persistently activated in ventricular myocytes from dogs with tachycardia-induced congestiveheart failure显示文摘 | CLEMO H F STAMBLER B S BAUMGARTEN C M | 1999 | CircRes1999，84，2： | 1 |
| 19 | Characterization of sustained atrial tachycardia in dogs with rapid ventricular pacing-induced heart failure 显示文摘 | Stambler BS Fenelon G Shepard RK | 2003 | J Cardiovasc Electrophysiol2003，14，5： | 1 |
| 20 | Tuberculosis abscess of the pancreas显示文摘 | Klibancer MI Bliss CM | 1982 | Gastroenterology1982，83，： | 1 |
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