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. 2004 Nov 16;110(20):3213-20. doi: 10.1161/01.CIR.0000147609.39780.02. Epub 2004 Nov 8.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • 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