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European Journal of Heart Failure 2007 9(10):974-985; doi:10.1016/j.ejheart.2007.06.012
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© 2007 European Society of Cardiology

Combined therapy with human cord blood cell transplantation and basic fibroblast growth factor delivery for treatment of myocardial infarction

Seung-Woo Choa,b, Il-Kwon Kimc,d, Suk Ho Bhanga,b, Boyoung Jounge, Young Jin Kimf, Kyung Jong Yood, Yoon-Sun Yangg, Cha Yong Choib and Byung-Soo Kima,*

a Department of Bioengineering, Hanyang University Seoul 133-791, Republic of Korea
b School of Chemical and Biological Engineering, Seoul National University Seoul 151-742, Republic of Korea
c Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine Seoul 120-752, Republic of Korea
d Division of Cardiovascular Surgery, Cardiovascular Center, Yonsei University College of Medicine Seoul 120-752, Republic of Korea
e Division of Cardiology, Cardiovascular Hospital and Research Institute, Yonsei University College of Medicine Seoul 120-752, Republic of Korea
f Department of Radiology, Yonsei University College of Medicine Seoul 120-752, Republic of Korea
g Department of Research and Development for Cellular Therapy, Medipost Biomedical Research Institute Yongin, 449-795, Republic of Korea

* Corresponding author. Tel.: +82 2 2220 0491; fax: +82 2 2298 4101. E-mail address: bskim{at}hanyang.ac.kr (B.-S. Kim).


  Abstract

Background: Transplanting cord blood-derived cells has been shown to augment neovascularization in ischaemic tissue.

Aim: To test whether sustained delivery of basic fibroblast growth factor (bFGF) enhances the efficacy of angiogenic cord blood mononuclear cell (CBMNC) transplantation therapy in treating myocardial infarction.

Methods: Three weeks after myocardial infarction, Sprague-Dawley rats were randomised to either injection of medium only (control), CBMNC transplantation, sustained bFGF delivery, or combined CBMNC transplantation and sustained bFGF delivery. Six weeks after treatment, tissue formation, neovascularization, and apoptotic activity in the infarct regions were evaluated by histology and immunohistochemistry. Left ventricular (LV) dimensions and function were evaluated by magnetic resonance imaging.

Results: Combined bFGF delivery and CBMNC transplantation significantly enhanced neovascularization in the ischaemic myocardium, as compared with either therapy alone. The enhanced neovascularization was likely due to increased VEGF and bFGF expression. The combined therapy also exhibited a reduced infarct area and apoptosis in the ischaemic myocardium, as compared with either individual therapy. The combined therapy did not attenuate LV dilation or increase ejection fraction significantly over either individual therapy.

Conclusion: This study demonstrates that sustained bFGF delivery enhances the angiogenic efficacy of CBMNC transplantation in rat myocardial infarction models.

Key Words: Neovascularization • Basic fibroblast growth factor • Cord blood mononuclear cell • Myocardial infarction

Received September 16, 2006; Revised April 7, 2007; Accepted June 25, 2007


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