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(Circulation. 2006;114:I-114 – I-119.)
© 2006 American Heart Association, Inc.

Cell Transplantation and Tissue Engineering

The Impact of the Capability of Circulating Progenitor Cell to Differentiate on Myocardial Salvage in Patients With Primary Acute Myocardial Infarction

Yasushi Numaguchi, MD, PhD; Takahito Sone, MD, PhD; Kenji Okumura, MD, PhD; Masakazu Ishii, MSc; Yasuhiro Morita, MD; Ryuji Kubota, MD; Kazuhiko Yokouchi, MD; Hajime Imai, MD; Mitsunori Harada, MD, PhD; Hiroyuki Osanai, MD, PhD; Takahisa Kondo, MD, PhD; Toyoaki Murohara, MD, PhD

From Nagoya University Graduate School of Medicine (Y.N., K.O., R.K., K.Y., T.K., T.M.), Department of Cardiology, and Nagoya University School of Medicine, Department of Medical Science of Proteases (Y.N., M.I.), Showa, Nagoya, Japan; Ogaki Municipal Hospital (T.S., Y.M.), Department of Cardiology, Minaminokawa, Ogaki, Gifu, Japan; Komaki Municipal Hospital (H.I.), Deparment of Cardiology, Jobushi, Komaki, Aichi, Japan; Kariya General Hospital (M.H.), Department of Cardiology, Sumiyoshi, Kariya, Aichi, Japan; Tosei General Hospital (H.O.), Department of Cardiology, Nishioiwake, Seto, Aichi, Japan.

Correspondence to Yasushi Numaguchi, Nagoya University Graduate School of Medicine, Department of Cardiology and Nagoya University School of Medicine, Department of Medical Science of Proteases, 65 Tsurumai, Showa, Nagoya 466-8550. Japan. E-mail numa2{at}med.nagoya-u.ac.jp

Background— Circulating endothelial progenitor cells (EPCs) are known to be involved in vasculogenesis and mobilized after acute myocardial infarction (AMI). To test the hypothesis that the angiogenic function of EPCs affects post-myocardial infarction (MI) myocardial salvage, we evaluated the number and potential differentiation of EPCs and compared these data with clinical parameters 6 months after MI.

Methods and Results— Consecutive 51 patients (age, 61±8 years, mean±SD) with primary AMI who were successfully treated with stenting were enrolled. EPC identified as CD45^low, CD34⁺, CD133⁺, and VEGFR2⁺ was quantified by a flow cytometry. The potential of EPCs to differentiate into endothelial cells (EPC differentiation) was also confirmed by the upregulation of CD31 and VEGFR2 after 7 days of culture. According to the proportion of EPC fraction, patients were divided into 2 groups (cut-off value=median). Although no difference was seen in myocardial damage shown by mean peak CK leakage and mean area at risk between the differentiated group (n=26) and nondifferentiated group (n=25), the number of attached cell was greater in differentiated group than in the nondifferentiated group (P=0.023). Left ventricular function and ischemic damaged area were assessed by scintigraphic images of ¹²³I-BMIPP in the acute phase and ^99mTc-tetrofosmin in the chronic phase. We found that a greater increase in myocardial salvage (P=0.0091), decrease in end-systolic volume (P=0.012), and recovery of ejection fraction (P=0.011) occurred in the group with differentiated EPCs than in the nondifferentiated group.

Conclusions— In patients with primary AMI, the capability of EPCs to differentiate influences the functional improvement and infarct size reduction, indicating that manipulation of EPCs could be a novel therapeutic target to salvage ischemic damage.

Key Words: ischemia • myocardial infarction • myocardial salvage • progenitor cell • reperfusion • scintigraphy