Recent Advances in Endothelial Progenitor Cells Toward Their Use in Clinical Translation
Open accessAbstract
Since the discovery of Endothelial Progenitor Cells (EPC) by Asahara and colleagues in 1997, an increasing number of preclinical studies have shown that EPC based therapy is feasible, safe, and efficacious in multiple disease states. Subsequently, this has led to several, mainly early phase, clinical trials demonstrating the feasibility and safety profile of EPC therapy, with the suggestion of efficacy in several conditions including ischemic heart disease, pulmonary arterial hypertension and decompensated liver cirrhosis. Despite the use of the common term "EPC," the characteristics, manufacturing methods and subset of the cell type used in these studies often vary significantly, rendering clinical translation challenging. It has recently been acknowledged that the true EPC is the endothelial colony forming cells (ECFC). The objective of this review was to summarize and critically appraise the registered and published clinical studies using the term "EPC," which encompasses a heterogeneous cell population, as a therapeutic agent. Furthermore, the preclinical data using ECFC from the PubMed and Web of Science databases were searched and analyzed. We noted that despite the promising effect of ECFC on vascular regeneration, no clinical study has stemmed from these preclinical studies. We showed that there is a lack of information registered on www.clinicaltrials.gov for EPC clinical trials, specifically on cell culture methods. We also highlighted the importance of a detailed definition of the cell type used in EPC clinical trials to facilitate comparisons between trials and better understanding of the potential clinical benefit of EPC based therapy. We concluded our review by discussing the potential and limitations of EPC based therapy in clinical settings.
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The major constraints associated with EPC therapy are the lack of a standardized production protocol, the prolonged culture time required to obtain a therapeutic dose owing to its low occurrence in peripheral blood and umbilical cord blood, and the restriction of autologous administration due to inherent immunogenicity.
“The major constraints associated with EPC therapy are the lack of a standardized production protocol, the prolonged culture time required to obtain a therapeutic dose owing to its low occurrence in PB and UCB, and the restriction of autologous administration due to inherent immunogenicity [69].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [69]
The Discussion identifies inconsistent EPC culture and characterization methods and immunogenicity of allogeneic EPCs as limitations. But its statement that low frequency in peripheral and cord blood necessitates long culture times and restricts treatment to autologous administration concerns ECFC therapy specifically, not EPC therapy generally. (LLM, conf=0.88)
Experimental — accuracy not yet measuredEPCs represent a small, heterogeneous progenitor cell population originating from bone marrow or peripheral blood, encompassing both early EPCs (myeloid angiogenic cells) and late EPCs (endothelial colony-forming cells).
“EPCs, as initially characterized by Asahara et al. in 1997, represent a small, heterogeneous progenitor cell population originating from bone marrow or peripheral blood, encompassing both early EPCs [myeloid angiogenic cells (MACs)] and late EPCs [endothelial colony-forming cells (ECFCs)] [68–70].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [69]
The Introduction identifies EPCs as a heterogeneous population encompassing early EPCs (including MACs) and late EPCs (including ECFCs), and credits Asahara et al. with pioneering the concept. The clinical-trials Results describe EPCs derived from bone marrow or peripheral blood. Our copy does not establish that EPCs are a small population. (LLM, conf=0.85)
Experimental — accuracy not yet measuredCo-culturing MSCs with EPCs induced differentiation into pericyte-like cells that stabilize newly formed vasculature.
“Furthermore, by co-culturing with EPCs, MSCs were induced to differentiate into pericyte-like cells, which act to stabilize the newly formed vasculature [69, 375].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [69]
The Discussion (page not available in our copy) says ECFCs can be combined with MSCs and reports that MSCs can differentiate into pericyte-like cells that stabilize formed vasculature. It does not say that co-culturing with EPCs induces that differentiation, so the claimed causal step is unsupported. (LLM, conf=0.86)
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- Authors
- Keighron, C., Lyons, C. J., Creane, M., O'Brien, T., & Liew, A.
- Affiliations
- Ollscoil na Gaillimhe – University of Galway (IE)
- Corresponding author
- Liew, Aaron
- Venue
- Frontiers in Medicine
- Publisher
- Frontiers Media SA
- Published
- 2018-12-18
- Volume
- 5
- Pages
- 354-354
- ISSN
- 2296-858X (ISSN-L)
- PMC
- PMC6305310
- OpenAlex
- W2904698475
- Cited by
- 74
- References
- 93
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 8 · 2023: 14 · 2022: 13 · 2021: 14 · 2020: 8 · 2019: 4 · 2018: 1
- FWCI
- 0.66
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Science Foundation Ireland (15/IA/3136)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- endothelial progenitor cells, endothelial colony-forming cells, cell therapy, clinical translation, cell culture, clinical trials, ischemic heart disease, pulmonary arterial hypertension, liver cirrhosis, vascular regeneration, cellular heterogeneity
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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