Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal ce...Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal cells(MSCs)exhibited greater therapeutic efficacy than CD146-MSCs.These cells enhance epithelial repair through nuclear factor kappa B/cyclooxygenase-2-associated paracrine signaling and secretion of pro-angiogenic factors.We concur that MSCs hold significant promise for ARDS treatment;however,the heterogeneity of cell products is a translational barrier.Phenotype-aware strategies,such as CD146 enrichment,standardized potency assays,and extracellular vesicle profiling,are essential for improving the consistency of these studies.Further-more,advanced preclinical models,such as lung-on-a-chip systems,may provide more predictive insights into the therapeutic mechanisms.This article underscores the importance of CD146+MSCs in ARDS,emphasizes the need for precision in defining cell products,and discusses how integrating subset selection into translational pipelines could enhance the clinical impact of MSC-based therapies.展开更多
Acute respiratory distress syndrome(ARDS)remains without effective targeted reparative therapies and continues to carry a high mortality rate.Here,we comment on a recent study by Zhang et al,who identify a CD146+subpo...Acute respiratory distress syndrome(ARDS)remains without effective targeted reparative therapies and continues to carry a high mortality rate.Here,we comment on a recent study by Zhang et al,who identify a CD146+subpopulation of mesenchymal stromal cells(MSCs)with superior reparative function in lipopolysaccharide-induced ARDS in mice.Compared with CD146-MSCs,CD146+MSCs secreted higher levels of reparative paracrine mediators,including hepatocyte growth factor,vascular endothelial growth factor,prostaglandin E2(PGE2),and angiopoietin 1,better preserved endothelial junctional proteins(VE-cadherin,zonula occludens-1),and more effectively modulated T cell and macrophage phenotypes.Mechanistic studies link these effects to a nuclear factor kappa B(NF-κB)/cyclooxygenase-2/PGE2 signaling axis,as pharmacologic blockade of NF-κB(caffeic acid phenethyl ester)abrogated the benefits.We place these results in the context of MSC heterogeneity research,highlight strengths(mechanistic depth,in vivo validation)and limitations(single animal model,reliance on cell lines rather than primary human cells),and propose next steps:Testing efficacy across diverse ARDS etiologies(viral,aspiration),validating effects in primary human alveolar and endothelial cells,delineating the CD146/NF-κB cascade,developing potency biomarkers(e.g.,PGE2),and performing rigorous safety profiling.Strategies to enrich or prime MSCs for CD146-associated NF-κB/cyclooxygenase-2/PGE2 program activity may provide a practical route to higher potency.展开更多
基金the Scientific and Technological Research Council of Türkiye(TÜBİTAK)Under the International Postdoctoral Research Fellowship Program(2219),No.1059B192400980the National Postdoctoral Research Fellowship Program(2218),No.122C158.
文摘Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal cells(MSCs)exhibited greater therapeutic efficacy than CD146-MSCs.These cells enhance epithelial repair through nuclear factor kappa B/cyclooxygenase-2-associated paracrine signaling and secretion of pro-angiogenic factors.We concur that MSCs hold significant promise for ARDS treatment;however,the heterogeneity of cell products is a translational barrier.Phenotype-aware strategies,such as CD146 enrichment,standardized potency assays,and extracellular vesicle profiling,are essential for improving the consistency of these studies.Further-more,advanced preclinical models,such as lung-on-a-chip systems,may provide more predictive insights into the therapeutic mechanisms.This article underscores the importance of CD146+MSCs in ARDS,emphasizes the need for precision in defining cell products,and discusses how integrating subset selection into translational pipelines could enhance the clinical impact of MSC-based therapies.
基金the Basic Research Program of Jiangsu Province(2024),No.BK20240907the“Lv Yang Jin Feng”Outstanding Doctor of Yangzhou,No.YZLYJFJH2023YXBS169the Top-Level Talents Support Program of Yangzhou University.
文摘Acute respiratory distress syndrome(ARDS)remains without effective targeted reparative therapies and continues to carry a high mortality rate.Here,we comment on a recent study by Zhang et al,who identify a CD146+subpopulation of mesenchymal stromal cells(MSCs)with superior reparative function in lipopolysaccharide-induced ARDS in mice.Compared with CD146-MSCs,CD146+MSCs secreted higher levels of reparative paracrine mediators,including hepatocyte growth factor,vascular endothelial growth factor,prostaglandin E2(PGE2),and angiopoietin 1,better preserved endothelial junctional proteins(VE-cadherin,zonula occludens-1),and more effectively modulated T cell and macrophage phenotypes.Mechanistic studies link these effects to a nuclear factor kappa B(NF-κB)/cyclooxygenase-2/PGE2 signaling axis,as pharmacologic blockade of NF-κB(caffeic acid phenethyl ester)abrogated the benefits.We place these results in the context of MSC heterogeneity research,highlight strengths(mechanistic depth,in vivo validation)and limitations(single animal model,reliance on cell lines rather than primary human cells),and propose next steps:Testing efficacy across diverse ARDS etiologies(viral,aspiration),validating effects in primary human alveolar and endothelial cells,delineating the CD146/NF-κB cascade,developing potency biomarkers(e.g.,PGE2),and performing rigorous safety profiling.Strategies to enrich or prime MSCs for CD146-associated NF-κB/cyclooxygenase-2/PGE2 program activity may provide a practical route to higher potency.
