Current concepts on endothelial stem cells definition, location, and markers.

Area of Science:

• Cardiovascular Biology
• Stem Cell Therapy
• Regenerative Medicine

Background:

• Ischemic vascular disease poses significant global health challenges, driving the need for effective vascular regeneration strategies.
• Endothelial stem/progenitor cells are a promising therapeutic avenue for repairing damaged vasculature and improving perfusion in ischemic tissues.
• Discrepancies in cell definitions and isolation methods have led to confusion and inconsistent clinical outcomes.

Purpose of the Study:

• To propose a stricter definition of endothelial stem cells based on stem cell biology principles.
• To review recent advancements and persistent challenges in endothelial stem cell therapy.
• To explore emerging evidence regarding the origin and niche of these critical cells.

Main Methods:

• Literature review of preclinical and clinical studies on endothelial stem cell therapy.
• Analysis of different endothelial stem/progenitor cell definitions and isolation techniques.
• Discussion of novel markers for identifying tissue-resident endothelial stem cells.

Main Results:

• Preclinical studies show promise, but clinical trials yield contradictory results, indicating significant therapeutic challenges.
• Emerging evidence suggests the vascular wall, not bone marrow, may be the primary niche for tissue-resident endothelial stem cells.
• Novel markers such as CD157, EPCR, and CD31low VEGFR2low IL33+ Sox9+ are identified for endothelial stem cell characterization.

Conclusions:

• A standardized definition and improved understanding of endothelial stem cell biology are crucial for therapeutic success.
• Addressing challenges in clinical translation is essential to harness the full potential of endothelial stem cell therapies.
• Identifying tissue-resident endothelial stem cells via novel markers may pave the way for more targeted and effective treatments for ischemic vascular disease.