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PMID: 15533859 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

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.

Circulation ·Vol. 110 ·No. 20 ·2004-11-16 ·Pages 3213-20

Wojakowski W, Tendera M, Michałowska A, Majka M, Kucia M, Maślankiewicz K, Wyderka R, Ochała A, Ratajczak MZ

Abstract

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). 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. 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.

MeSH Terms
Adult Angina Pectoris/blood,physiopathology Antigens, CD34/analysis Antigens, Differentiation/analysis Blood Cell Count Chemokine CXCL12 Chemokines, CXC/blood,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,physiology Male Middle Aged Multipotent Stem Cells/chemistry,physiology Muscles/cytology Myocardial Infarction/blood,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
Chemicals
Antigens, CD34 Antigens, Differentiation CXCL12 protein, human Chemokine CXCL12 Chemokines, CXC Cytokines Interleukin-6 Receptors, CXCR4 Vascular Endothelial Growth Factor A Granulocyte Colony-Stimulating Factor Hepatocyte Growth Factor Proto-Oncogene Proteins c-kit Proto-Oncogene Proteins c-met
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Wojakowski Wojciech
Third Division of Cardiology, Silesian School of Medicine, 45-47 Ziołowa St, 40-635 Katowice, Poland. [email protected]
Tendera Michał
Michałowska Anna
Majka Marcin
Kucia Magdalena
Maślankiewicz Katarzyna
Wyderka Rafał
Ochała Andrzej
Ratajczak Mariusz Z
Article Info
Journal
Circulation
Abbr.
Circulation
ISSN
1524-4539
Published
2004-11-16
Epub
2004-00-08
Pages
3213-20
Language
English
Region
United States
NLM ID
0147763
Subset
IM
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