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. 2020 Nov;9(11):1344-1352.
doi: 10.1002/sctm.20-0141. Epub 2020 Jul 18.

Human endothelial colony-forming cells in regenerative therapy: A systematic review of controlled preclinical animal studies

Gary Liao  1   2 , Katina Zheng  2 , Risa Shorr  3 , David S Allan  1   2
Affiliations

Human endothelial colony-forming cells in regenerative therapy: A systematic review of controlled preclinical animal studies

Gary Liao et al. Stem Cells Transl Med. 2020 Nov.

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.

Keywords: ECFCs; controlled studies; preclinical; regenerative medicine; systematic review.

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Conflict of interest statement

D.S.A. declared consultant/advisory role for Canadian Blood Services. All the other authors declared no potential conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Complete Medina Criteria compared to the modified Medina Criteria. Figure adapted from the Medina et al study 8
FIGURE 2
FIGURE 2
PRISMA diagram outlining the screening process. Specific reasons for exclusion are included for the full‐text assessment
FIGURE 3
FIGURE 3
Radar chart depicting the distribution of surface markers being reported across all articles. This chart is an aggregate of all markers reported within both the primary article and references protocols or previous studies
See this image and copyright information in PMC

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