Microvascular mural cell functionality of human embryonic stem cell-derived mesenchymal cells.

Area of Science:

• Stem cell biology
• Vascular biology
• Regenerative medicine

Background:

• Perivascular cells are crucial for blood vessel maturation but their biology is poorly understood.
• Large vessel smooth muscle cells are well-studied, but knowledge of mural cell function is limited.
• Human embryonic stem cells (hES-MC) were developed to investigate perivascular cell function.

Purpose of the Study:

• To determine if hES-MC can function as perivascular mural cells.
• To characterize the molecular and functional properties of hES-MC in vitro.
• To assess the role of hES-MC in endothelial cell network stabilization.

Main Methods:

• Teratoma formation assay in SCID mice.
• Microarray analysis for gene expression profiling.
• Stimulation with growth factors (PDGF-BB, TGFβ1) and pathway inhibition (SB525334, Alk5 dominant negative).
• Coculture with human umbilical vein endothelial cells (HUVEC) in 3D collagen I-fibronectin.
• Laser confocal microscopy.

Main Results:

• hES-MC are non-teratogenic and exhibit consistent gene expression patterns.
• hES-MC express platelet-derived growth factor receptor β and migrate in response to PDGF-BB.
• TGFβ1 induces contractile protein expression in hES-MC via the TGFβR1/Alk5 pathway.
• hES-MC cocultured with HUVEC enhance endothelial network integrity through paracrine signaling and direct contact.
• hES-MC possess molecular machinery characteristic of perivascular progenitor cells.

Conclusions:

• hESC-derived mesenchymal cells (hES-MC) demonstrate characteristics of perivascular progenitor cells.
• hES-MC can functionally contribute to the stabilization of endothelial cell networks in vitro.
• These findings support the potential of hES-MC in vascular research and regenerative medicine.