Human endothelial colony-forming cells in regenerative therapy: A systematic review of controlled preclinical animal studies. (18th July 2020)

• Record Type: Journal Article
• Authors: Liao, Gary; Zheng, Katina; Shorr, Risa; Allan, David S.
• Is Part Of: Stem cells translational medicine. Volume 9:Number 11(2020)
• Page Start: 1344
• Page End: 1352
• Publication Date: 2020-07-18
• Subjects: controlled studies -- ECFCs -- preclinical -- regenerative medicine -- systematic review; Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.1002/sctm.20-0141
• Languages: English
• ISSNs: 2157-6564

Abstract

Abstract: Endothelial colony-forming cells (ECFCs) hold significant promise as candidates for regenerative therapy of vascular injury. Existing studies remain largely preclinical and exhibit marked design heterogeneity. A systematic review of controlled preclinical trials of human ECFCs is needed to guide future study design and to accelerate clinical translation. A systematic search of Medline and EMBASE on 1 April 2019 returned 3131 unique entries of which 66 fulfilled the inclusion criteria. Most studies used ECFCs derived from umbilical cord or adult peripheral blood. Studies used genetically modified immunodeficient mice (n = 52) and/or rats (n = 16). ECFC phenotypes were inconsistently characterized. While >90% of studies used CD31+ and CD45−, CD14− was demonstrated in 73% of studies, CD146+ in 42%, and CD10+ in 35%. Most disease models invoked ischemia. Peripheral vascular ischemia (n = 29), central nervous system ischemia (n = 14), connective tissue injury (n = 10), and cardiovascular ischemia and reperfusion injury (n = 7) were studied most commonly. Studies showed predominantly positive results; only 13 studies reported ≥1 outcome with null results, three reported only null results, and one reported harm. Quality assessment with SYRCLE revealed potential sources of bias in most studies. Preclinical ECFC studies are associated with benefit across several ischemic conditions in animal models, although combining results is limited by marked heterogeneity in study design. In particular, characterization of ECFCs varied and aspects of reporting introduced risk of bias in most studies. More studies with greater focus on standardized cell characterization and consistency of the disease model are needed. : Abstract : Marked heterogeneity in the characterization of endothelial colony-forming cells (ECFCs) exist across all included (n = 66) preclinical controlled studies. This radar chart depicts the distribution of surface markers reported and aggregates all markers reported within both the primary article and references, protocols, or previous studies. It highlights the necessity for future studies to adhere to standardized criteria for characterization of ECFCs.