Stem cell therapy for COVID-19 and other respiratory diseases:Global trends of clinical trials

Respiratory diseases,including coronavirus disease 2019 and chronic obstructive pulmonary disease(COPD),are leading causes of global fatality.There are no effective and curative treatments,but supportive care only.Cell therapy is a promising therapeutic strategy for refractory and unmanageable pulmonary illnesses,as proved by accumulating preclinical studies.Stem cells consist of totipotent,pluripotent,multipotent,and unipotent cells with the potential to differentiate into cell types requested for repair.Mesenchymal stromal cells,endothelial progenitor cells,peripheral blood stem cells,and lung progenitor cells have been applied to clinical trials.To date,the safety and feasibility of stem cell and extracellular vesicles administration have been confirmed by numerous phase I/II trials in patients with COPD,acute respiratory distress syndrome,bronchial dysplasia,idiopathic pulmonary fibrosis,pulmonary artery hypertension,and silicosis.Five routes and a series of doses have been tested for tolerance and advantages of different regimes.In this review,we systematically summarize the global trends for the cell therapy of common airway and lung diseases registered for clinical trials.The future directions for both new clinical trials and preclinical studies are discussed.

Epithelial Sodium and Chloride Channels and Asthma

Objective：To focus on the asthmatic pathogenesis and clinical manifestations related to epithelial sodium channel （ENaC）/chlorine ion channel.Data Sources：The data analyzed in this review were the English articles from 1980 to 2015 from journal databases,primarily PubMed and Google Scholar.The terms used in the literature search were：（1） ENaCs;cystic fibrosis （CF） transmembrane conductance regulator （CFTR）;asthma/asthmatic,（2） ENaC/sodium salt;CF;asthma/asthmatic,（3） CFTR/chlorine ion channels;asthma/asthmatic,（4） ENaC/sodium channel/scnn1a/scnn1b/scnn1g/scnn1d/amiloride-sensitive/amiloride-inhibtable sodium channels/sodium salt;asthma/asthmatic,lung/pulmonary/respiratory/tracheal/alveolar,and （5） CFTR;CF;asthma/asthmatic （ti）.Study Selection：These studies included randomized controlled trials or studies covering asthma pathogenesis and clinical manifestations related to ENaC/chlorine ion channels within the last 25 years （from 1990 to 2015）.The data involving chronic obstructive pulmonary disease and CF obtained from individual studies were also reviewed by the authors.Results：Airway surface liquid dehydration can cause airway inflammation and obstruction.ENaC and CFTR are closely related to the airway mucociliary clearance.Ion transporters may play a critical role in pathogenesis of asthmatic exacerbations.Conclusions：Ion channels have been the center of many studies aiming to understand asthmatic pathophysiological mechanisms or to identify therapeutic targets for better control of the disease.

间充质干细胞的恶性转化研究进展

间充质干细胞(MSCs)是一种多能干细胞,在体外的特定诱导条件下可以分化为多种组织细胞。其独特的生物学特性,在组织损伤修复与肿瘤靶向治疗等临床应用方面展现出广阔的应用前景。然而有研究表明MSCs在应用过程中有可能发生恶性转化。本文主要对MSCs发生恶性转化的影响因素、分子机制以及如何预防MSCs发生恶性转化的新近研究进行综述。

Fibrinolytic niche is required for alveolar type 2 cell-mediated alveologenesis via a uPA-A6-CD44^(+)-ENaC signal cascade

Dear Editor,COVID-19,SARS,and MERS are featured by suppressed lungfibrinolysis.The primary objective of this study was to decipherthe role of the fibrinolytic niche in the progenitor alveolar type 2(AT2)cell-mediated re-alveolarization.The expression of Piau inAT2 cells has been confirmed at the mRNA,protein,and functionallevel across species.We employed influenza-infected&Plau^(-/-)mice,3D organoids,and polarized monolayers to track AT2 fate.We found a marked reduction in total AT2 cells and CD44^(+)subpopulation when the fibrinolytic niche was disrupted.

SCNN1基因突变与呼吸系统疾病

SCNN1是编码上皮钠离子通道（ENaC）蛋白的一类基因，目前发现的已经被克隆的哺乳类SCNN1基因包括SCNN1A、SCNN1B、SCNN1G、SCNN1D，分别表达ENaC的α、β、γ、δ亚基。ENaC在维持钠、水平衡中起着重要作用，而SCNN1基因的突变将会影响ENaC的结构与功能，进而导致一系列的疾病。随着研究的深入，人们对SCNN1基因的结构与功能也有了进一步的认识。这篇文章将综述SCNN1基因结构和功能以及它的突变引起的呼吸系统疾病，目的是总结SCNN1基因突变型与呼吸系统疾病表型的关系。