Mobilization of Bone Marrow-Derived Oct-4 ⁺SSEA-4 ⁺ Very Small Embryonic-Like Stem Cells in Patients with Acute Myocardial Infarction

Abstract

Objective

Assessment of the mobilization of non-hematopoietic very small embryonic-like stem cells (VSEL) in acute myocardial infarction (MI).

Background

Acute MI induces mobilization of bone marrow stem cells. Recently rare population of VSELs, expressing markers of embryonic pluripotent stem cells (PSC) was identified in adult murine bone marrow and human umbilical cord blood.

Methods

31 pts with acute MI and 30 healthy subjects (CTRL) were enrolled. Blood was sampled on admission, after 24 hours and 5 days later. Erythrocytes were lysed and lin ^-CD45 ^- VSELs were isolated using a live cell sorting system (FACSAria).

Results

In healthy subjects the median number of circulating VSEL was very low [0.8 (0-1.3] cells/μL. In acute MI VSELs were mobilized early [2.7 (0.2-3.9) cells/μL; p<0.001), and remained elevated after 24 hrs and 5 days [4.7 (0.2-6.4); p<0.003 and 2.6 (0.3-3.6) cells/μL; p<0.03, respectively). The mobilization of VSEL was significantly reduced in patients older than 50 years and with diabetes in comparison to younger and non-diabetic patients. Circulating VSELs were small (7-8 μm) and enriched in mRNA of PSC markers (Oct-4, Nanog), cardiac lineage (GATA-4, Nkx2.5/Csx, MEF2C) and endothelial (VE-cadherin) markers. The presence of PSC markers (Oct-4, SSEA-4) and chemokine receptor CXCR4 in circulating VSELs was confirmed at the protein level by immunofluorescent staining and ImageStream system (ISS) analysis.

Conclusion

Acute MI induced mobilization of very small embryonic-like stem cells expressing pluripotent markers, early cardiac and endothelial markers and chemokine receptor CXCR4.