High NESTIN Expression Marks the Endosteal Capillary Network in Human Bone Marrow

Area of Science:

• Hematology
• Vascular Biology
• Stem Cell Biology

Background:

• The bone marrow (BM) microenvironment, or niche, is crucial for hematopoiesis.
• BM niches are categorized as endosteal or central, with distinct vascular characteristics observed in mice but less understood in humans.

Purpose of the Study:

• To investigate the architecture and vascular components of the human bone marrow niche.
• To identify and characterize specific blood vessel types and their association with hematopoietic stem/progenitor cells.

Main Methods:

• Utilized immunohistochemistry and immunofluorescence on human BM trephines.
• Employed markers like NESTIN, CD146, and αSMA to label endothelial cells and perivascular cells.
• Conducted image analysis on approximately 300 microphotographs to quantify and localize vessels.

Main Results:

• Detected high NESTIN expression in endothelial cells of human arteries and endosteal arterioles.
• Identified novel NESTIN+ capillary-like tubes (NCLTs) located near bone trabeculae.
• NCLTs were found in close proximity to hematopoietic stem/progenitor cells and lacked surrounding perivascular cells.

Conclusions:

• Confirmed NESTIN expression in human bone marrow endothelial cells of arteries and arterioles, aligning with murine models.
• Proposed NCLTs as transitional vessels potentially regulating human hematopoiesis due to their unique characteristics and location.
• Highlighted the importance of understanding human BM vascular architecture for hematopoiesis research.