© 2008 European Society of Cardiology
Transplantation of adipose derived stromal cells is associated with functional improvement in a rat model of chronic myocardial infarction
a Hematology and Cell Therapy and Foundation for Applied Medical Research, Division of Cancer, University of Navarra Pamplona, Spain
b UMR 5241 CNRS UPS, Institut Louis Bugnard Toulouse, France
c Department of Cardiology and Cardiovascular Surgery, Clínica Universitaria Pamplona, Spain
d Department of Nuclear Medicine and MicroPET Research Unit CIMA-CUN, Clínica Universitaria Pamplona, Spain
* Corresponding authors. Casteilla is to be contacted at UMR-CNRS 5241 IFR31, CHU Rangueil 1 avenue Jean Poulhès, 31432 Toulouse cedex 4, France. Tel.: +33 5 62 17 08 91; fax: +33 5 62 17 09 05. Prósper, Hematology and Cell Therapy Area, Clínica Universitaria, Av Pío XII 36, 31008 Pamplona, Spain. Tel.: +34 948 255400; fax: +34 948 296500. E-mail addresses: casteil{at}toulouse.inserm.fr (L. Casteilla), fprosper{at}unav.es (F. Prósper).
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Abstract |
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Aims: To determine the effect of transplantation of undifferentiated and cardiac pre-differentiated adipose stem cells compared with bone marrow mononuclear cells (BM-MNC) in a chronic model of myocardial infarction.
Methods: Ninety-five Sprague–Dawley rats underwent left coronary artery ligation and after 1month received by direct intramyocardial injection either adipose derived stem cells (ADSC), cardiomyogenic cells (AD-CMG) or BM-MNC from enhanced-Green Fluorescent Protein (eGFP) mice. The control group was treated with culture medium. Heart function was assessed by echocardiography and 18F-FDG microPET. Cell engraftment, differentiation, angiogenesis and fibrosis in the scar tissue were also evaluated by (immuno)histochemistry and immunofluorescence.
Results: One month after cell transplantation, ADSC induced a significant improvement in heart function (LVEF 46.3±9.6% versus 27.7±8% pre-transplant) and tissue viability (64.78±7.2% versus 55.89±6.3% pre-transplant). An increase in the degree of angiogenesis and a decrease in fibrosis were also detected. Although transplantation of AD-CMG or BM-MNC also had a positive, albeit smaller, effect on angiogenesis and fibrosis in the infarcted hearts, this benefit did not translate into a significant improvement in heart function or tissue viability.
Conclusion: These results indicate that transplantation of adipose derived cells in chronic infarct provides a superior benefit to cardiac pre-differentiated ADSC and BM-MNC.
Key Words: Cell therapy • Stem cells • Chronic ischaemic heart failure • angiogenesis
Received December 11, 2007; Revised February 26, 2008; Accepted March 26, 2008
1 Contributed equally to this study and should be considered equal first authors.
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