Endothelial and circulating progenitor cells as prognostic biomarkers of stroke: A systematic review and meta-analysis

Abstract

Purpose: Endothelial progenitor cells (EPCs) are biomarkers of neurovascular repair in cerebral vascular disease (CVD). Low quantification of EPCs and/or their dysfunction has been associated with stroke severity and post-stroke functionality. This systematic review (SR) and meta-analysis aimed to analyze whether EPC quantification contributes to stroke severity and functional prognosis. Methods: Articles were selected from the PubMed, ScienceDirect, and Ovid MEDLINE databases, according to the guidelines of the PRISMA 2020 [1] statement. Detailed observational studies of samples from subjects with a clinical diagnosis of CVD (ischemic stroke-IS, hemorrhagic stroke-HS, or transient ischemic attack-TIA) aged >45 years during 2003-2023 were included. Evaluation of study quality was based on the Critical Appraisal Skills Programme checklist(Santamaria, 2017 [2]). Results: We included 22 articles in our SR. Patients with IS and good functional outcomes had higher EPC levels during the first week of admission than those with worse functional outcomes. Higher EPC levels were associated with reduced infarct growth, improved NIHSS scores at 48 h (OR 0.8; 95 % CI: 0.72-0.90; p < 0.0002) 7 (r =-0.607; p < 0.0001), and 90 days (r =-0.570; p < 0.0001), with a negative correlation between EPC levels and NIHSS score (overall pooled r =-0,32, 95 % CI:-0.39-0.24), and good functional outcomes with better mRS scores at 24 h, 3, 6, and 12 months (overall pooled SMD 4.51, CI 95 %: 0.70-0.83). Lower EPC quantification and worse functional outcomes during admission were predictors of IS recurrence. Higher EPC levels were associated with better functional outcomes and lower bleeding volumes in patients with HS and were protective markers for the progression high-risk TIA. Conclusion: EPCs seems to be predictive biomarkers of better clinical outcomes in patients with CVD, exhibiting lower severity (NIHSS) and better functional prognosis (mRS).