Stem cells, extracellular vesicles, and cell-free strategies in pulmonary arterial hypertension: a bibliometric study, 2006–2026

Pulmonary arterial hypertension (PAH) remains a high-mortality vasculopathy for which no current therapy reverses established vascular remodeling. Stem cell-based and cell-free extracellular vesicle (EV) therapies are promising disease-modifying strategies, yet prior PAH bibliometric studies have not treated this stem-cell-to-cell-free arc as a dedicated, continuous research front. We analyzed 891 articles and reviews (1 January 2006 to 15 March 2026) from the Web of Science Core Collection and PubMed using CiteSpace, VOSviewer, R bibliometrix, and logistic growth modeling. Annual output grew steeply to 2012 and has since held a level of about 50 publications a year, with no trend over 2013–2025 (slope +0.44 publications per year, 95% CI −0.49 to +1.37). Cumulative output followed an S-shaped logistic trajectory ( R 2 = 0.860), but the fitted saturation capacity is not identified by these data and is reported as indicative only. Co-citation, clustering and keyword-burst analyses support a descriptive three-phase framework of the field's development: endothelial progenitor cell-based replacement (2006–2012), the expansion of mesenchymal stromal cell (MSC) research (2013–2021), and a cell-free EV/exosome phase (2022–2026) marked by the strongest keyword burst in the dataset (extracellular vesicles, 12.55) and by active bursts for exosomes (6.80) and endothelial dysfunction (6.57). The United States (273) and China (223) led output, with Stanford University, Stewart D.J., and Humbert M. anchoring the knowledge network. Manufacturing standardization, targeting efficiency, and large-scale clinical evidence remain unresolved, and no phase III trial has been completed for any stem cell- or EV-based product. To our knowledge, these findings provide the first quantitative mapping of this stem-cell-to-cell-free transition in PAH, and identify the directions in which research attention is concentrating.