Mobilization of CD34/CXCR4+, CD34/CD117+, c-met+ stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction.
BACKGROUND
Adult stem cells can contribute to myocardial regeneration after ischemic injury. Bone marrow and skeletal muscles contain a population of CXCR4+ cells expressing genes specific for muscle progenitor cells that can be mobilized into the peripheral blood. The aims of the study were (1) to confirm the presence of early tissue-committed cells expressing cardiac, muscle, and endothelial markers in populations of mononuclear cells in peripheral blood and (2) to assess the dynamics and magnitude of the mobilization of CD34+, CD117+, CXCR4+, c-met+, CD34/CD117+, and CD34/CXCR4+ stem cells into peripheral blood in relation to inflammatory and hematopoietic cytokines in patients with ST-segment-elevation acute myocardial infarction (STEMI).


RESULTS
Fifty-six patients with STEMI (<12 hours), 39 with stable angina, and 20 healthy control subjects were enrolled. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used for detection of tissue-specific markers. The number of the cells was assessed by use of a flow cytometer on admission, after 24 hours, and after 7 days. RT-PCR revealed increased expression of mRNA (up to 3.5-fold increase) for specific cardiac (GATA4, MEF2C, Nkx2.5/Csx), muscle (Myf5, Myogenin, MyoD), and endothelial (VE-cadherin, von Willebrand factor) markers in peripheral blood mononuclear cells. The number of CD34/CXCR4+ and CD34/CD117+ and c-met+ stem cells in peripheral blood was significantly higher in STEMI patients than in stable angina and healthy subjects, peaking on admission, without further significant increase after 24 hours and 7 days.


CONCLUSIONS
The study demonstrates in the setting of STEMI a marked mobilization of mononuclear cells expressing specific cardiac, muscle, and endothelial markers as well as CD34/CXCR4+ and CD34/CD117+ and c-met+ stem cells and shows that stromal cell-derived factor-1 is an important factor influencing the mobilization.
Wojakowski
Wojciech
W
Third Division of Cardiology, Silesian School of Medicine, 45-47 Ziołowa St, 40-635 Katowice, Poland. wojwoj@mp.pl
Tendera
Michał
M
Michałowska
Anna
A
Majka
Marcin
M
Kucia
Magdalena
M
Maślankiewicz
Katarzyna
K
Wyderka
Rafał
R
Ochała
Andrzej
A
Ratajczak
Mariusz Z
MZ
D000328:Adult; D000787:Angina Pectoris / Q000097:blood / Q000503:physiopathology; D018952:Antigens, CD34 / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis*; D001772:Blood Cell Count; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000097:blood / Q000502:physiology; D016207:Cytokines / Q000097:blood*; D004727:Endothelium / Q000166:cytology; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D039902:Multipotent Stem Cells / Q000737:chemistry / Q000502:physiology*; D009132:Muscles / Q000166:cytology; D009203:Myocardial Infarction / Q000097:blood* / Q000503:physiopathology; D009206:Myocardium / Q000166:cytology; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis; D019718:Receptors, CXCR4 / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D018952:Antigens, CD34; D000943:Antigens, Differentiation; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D016207:Cytokines; D015850:Interleukin-6; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; D016179:Granulocyte Colony-Stimulating Factor; D017228:Hepatocyte Growth Factor; D019009:Proto-Oncogene Proteins c-kit; D019859:Proto-Oncogene Proteins c-met