Yonsei Med J.  2010 Jan;51(1):69-76. 10.3349/ymj.2010.51.1.69.

Therapeutic Potential of Human Adipose Stem Cells in a Rat Myocardial Infarction Model

Affiliations
  • 1Department of Radiology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Korea.
  • 2Department of Pathology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Korea.
  • 3Department of Cardiology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Korea.
  • 4Department of Thoracic and Cardiovascular Surgery, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Korea. phenix@catholic.ac.kr
  • 5Clinical Research Institute, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Korea.

Abstract

PURPOSE
Stem cell transplantation is expected to have good effects in the treatment of myocardial infarction (MI). We tested the effect of the transplantation of human adipose-derived cells (ASCs) in Sprague-Dawley (SD) rats with myocardial infarctions. MATERIALS AND METHODS: ASCs were isolated from the waste of elective abdominal surgery. The MI model was set up in SD rats by permanent ligation of the left anterior descending coronary artery. One week after MI, either 1 x 10(6) ASCs or an equal volume of phosphate-buffered saline (PBS) was injected into the infarct zone. Cardiac function was assessed by echocardiography, 1 day, 1 week, 2 weeks, and 4 weeks after treatment. Four weeks after transplantation, immunohistochemistry was performed. RESULTS: Left ventricular function, including fractional shortening (FS), and ejection fraction (EF) showed a significant improvement in the ASCs transplantation group compared to the PBS group 4 weeks after treatment (p < 0.05). The anterior wall thickness of the left ventricle was significantly thicker in the ASCs transplantation group compared to the PBS group (p < 0.01). Multiple troponin T staining, and irregular, small amounts of connexin 43 expression also was observed in the ASCs transplantation group. Infarcted myocardium showed higher capillary density in the ASCs transplantation group than in the PBS injected group (p < 0.01). CONCLUSION: This study provides encouraging evidence that transplantation of ASCs can improve cardiac function of infarct myocardium in rat models with a limitation of cardiac remodeling, improved wall thickness, and increased neovascularization.

Keyword

Myocardial infarction; stem cells; transplantation

MeSH Terms

Adipose Tissue/*cytology
Animals
Cells, Cultured
Disease Models, Animal
Echocardiography
Humans
Immunohistochemistry
Male
Mesenchymal Stem Cell Transplantation/*methods
Myocardial Infarction/metabolism/*therapy
Rats
Rats, Sprague-Dawley
Ventricular Function, Left

Figure

  • Fig. 1 Flow-cytometric analysis of adult adipose cells expanded to three passages. Most of the ASCs expressed CD44 and CD29, and did not express for CD34, CD45, HLADR and c-kit. ASCs, adipose-derived cells.

  • Fig. 2 Echocardiographic images after treatment. M-mode echocardiographic images demonstrating an increase in anterior wall thickening in the left ventricle and an improvement of ventricular function in the ASC transplantation group at the top images. Similar images representing post-infarction remodeling with left ventricular dilatation of the PBS group in middle. Echocardiographic images in the control sham operation group at the bottom. ASCs, adipose-derived cells; PBS, phosphate-buffered saline.

  • Fig. 3 H & E staining (A,×400) and immunohistochemical staining of connexin 43 (B,×100), troponin T (C,×100) and α-smooth muscle actin (D,×100) of the three groups. ASCs, adipose-derived cells; PBS, phosphate-buffered saline.


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