Hepatocyte growth factor mobilizes non-bone marrow-derived circulating mesoangioblasts

Area of Science:

• Regenerative Medicine
• Cardiovascular Biology
• Stem Cell Biology

Background:

• Endogenous progenitor cells can repair ischemic tissue.
• Circulating mesoangioblasts (cMABs) expressing endothelial markers were previously identified in children.
• The mobilization mechanisms and origin of cMABs remained unclear.

Purpose of the Study:

• To investigate the mobilization of circulating mesoangioblasts (cMABs) in adults undergoing heart surgery.
• To identify factors and mechanisms responsible for cMAB mobilization.
• To explore the therapeutic potential of cMABs in cardiac repair.

Main Methods:

• Analysis of circulating CD73(+)CD45(-)KDR(+) cMABs in adult patients with or without cardiopulmonary bypass (CPB).
• Enrichment analysis of cMABs in coronary sinus blood.
• Histological examination of cardiac tissue for CD73(+) cells.
• Cytokine profiling of serum samples and in vitro/in vivo stimulation assays using hepatocyte growth factor (HGF).

Main Results:

• Cardiopulmonary bypass (CPB) significantly mobilizes cMABs, peaking at the end of surgery.
• Off-pump surgery does not induce cMAB mobilization, suggesting CPB-induced stress is a trigger.
• cMABs are enriched in the coronary sinus and detected around cardiac vessels, indicating the heart as a niche.
• Hepatocyte growth factor (HGF) levels significantly increase during maximal cMAB mobilization.
• HGF directly stimulates cMAB migration and increases cMABs in vivo in rats.

Conclusions:

• Hepatocyte growth factor (HGF) induces the mobilization of non-hematopoietic progenitor cells with cardiac repair potential.
• The heart serves as a niche for these progenitor cells.
• HGF's role in progenitor cell mobilization presents a promising therapeutic avenue for ischemic heart disease.