Heydari Kimia, Johnson Carrie, Diane Cooper I, Hersi Kadija, Tanba Carl, Sun Junfeng, Solomon Michael A, Elinoff Jason M
Critical Care Medicine Department NIH Clinical Center, National Institutes of Health Bethesda Maryland USA.
National Institutes of Health Library Bethesda Maryland USA.
Pulm Circ. 2025 Mar 20;15(1):e70065. doi: 10.1002/pul2.70065. eCollection 2025 Jan.
Pulmonary arterial hypertension (PAH) is characterized by progressive narrowing and obliteration of distal, pre-capillary pulmonary vessels. Yet, noninvasive biomarkers that reflect this disease-defining process are lacking. A systematic review of PAH studies that measured circulating progenitor cells (CPCs) or circulating endothelial cells (CECs) in PAH by flow cytometry was performed to understand how future studies, leveraging state-of-the-art single-cell analyses, can advance the field. The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews. Of the 2422 studies identified, 20 met inclusion criteria. Nineteen studies measured CPCs by flow cytometry, only one study examined CECs. A total of 647 PAH patients were included across all 19 CPC studies. Marker schemes chosen to define CPCs, and the methods of flow cytometry used, varied significantly across studies. Meta-analysis of a subgroup of CPC studies ( = 8) similarly identified a significant amount of heterogeneity even amongst studies using the same marker scheme. In conclusion, a systematic review of CPC studies in PAH patients reveals the limitations of the current literature. Future studies should include contemporary risk assessments, disease duration, reporting of comorbid conditions, and serial sampling over time. Furthermore, methods that incorporate best practices for detecting rare cell populations by flow cytometry are essential and should be reported in sufficient detail in future publications. With the emergence of single-cell technologies, future studies of circulating progenitor and endothelial cells in PAH remain relevant and may incorporate several insights from the current review to build upon the existing literature.
肺动脉高压（PAH）的特征是远端毛细血管前肺血管逐渐变窄和闭塞。然而，目前缺乏能够反映这一疾病特征性过程的非侵入性生物标志物。我们对通过流式细胞术测量PAH患者循环祖细胞（CPCs）或循环内皮细胞（CECs）的PAH研究进行了系统综述，以了解未来利用先进的单细胞分析技术的研究如何推动该领域的发展。本研究按照系统综述的首选报告项目进行。在检索到的2422项研究中，有20项符合纳入标准。19项研究通过流式细胞术测量CPCs，只有1项研究检测了CECs。所有19项CPC研究共纳入了647例PAH患者。不同研究中用于定义CPCs的标志物方案以及所使用的流式细胞术方法差异很大。对一组CPC研究（n = 8）的荟萃分析同样发现，即使在使用相同标志物方案的研究中也存在大量异质性。总之，对PAH患者CPC研究的系统综述揭示了当前文献的局限性。未来的研究应包括当代风险评估、疾病持续时间、合并症报告以及随时间的系列采样。此外，采用流式细胞术检测稀有细胞群体的最佳实践方法至关重要，并且应在未来的出版物中详细报告。随着单细胞技术的出现，未来对PAH患者循环祖细胞和内皮细胞的研究仍然具有重要意义，并且可能会纳入本综述中的一些见解，以在现有文献的基础上进一步发展。
