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

• Published in: Circulation (New York, N.Y.) Vol. 110; no. 20; pp. 3213 - 3220
• Main Authors: Wojakowski, Wojciech, Tendera, Michał, Michałowska, Anna, Majka, Marcin, Kucia, Magdalena, Maślankiewicz, Katarzyna, Wyderka, Rafał, Ochała, Andrzej, Ratajczak, Mariusz Z.
• Format: Journal Article
• Language: English
• Published: United States 16.11.2004
• Subjects: Adult; Angina Pectoris - blood; Angina Pectoris - physiopathology; Antigens, CD34 - analysis; Antigens, Differentiation - analysis; Blood Cell Count; Chemokine CXCL12; Chemokines, CXC - blood; Chemokines, CXC - physiology; Cytokines - blood; Endothelium - cytology; Female; Flow Cytometry; Follow-Up Studies; Granulocyte Colony-Stimulating Factor - blood; Hepatocyte Growth Factor - blood; Humans; Inflammation - blood; Interleukin-6 - blood; Leukocytes, Mononuclear - chemistry; Leukocytes, Mononuclear - physiology; Male; Middle Aged; Multipotent Stem Cells - chemistry; Multipotent Stem Cells - physiology; Muscles - cytology; Myocardial Infarction - blood; Myocardial Infarction - physiopathology; Myocardium - cytology; Proto-Oncogene Proteins c-kit - analysis; Proto-Oncogene Proteins c-met - analysis; Receptors, CXCR4 - analysis; Reverse Transcriptase Polymerase Chain Reaction; Vascular Endothelial Growth Factor A - blood
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/01.CIR.0000147609.39780.02

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). Methods and 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.