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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:e192.)
© 2004 American Heart Association, Inc.

Vascular Biology

Molecular Evaluation of Endothelial Progenitor Cells in Patients With Ischemic Limbs

Therapeutic Effect by Stem Cell Transplantation

Koji Yamamoto; Takahisa Kondo; Satoshi Suzuki; Hideo Izawa; Masayoshi Kobayashi; Nobuhiko Emi; Kimihiro Komori; Tomoki Naoe; Junki Takamatsu; Toyoaki Murohara

From the Departments of Transfusion Medicine (K.Y., S.S., J.T.), Cardiology (T.K., H.I., T.M.), Vascular Surgery (M.K., K.K.), and Hematology (N.E., T.N.), Nagoya University Hospital, Nagoya, Japan.

Correspondence to Dr K. Yamamoto, Department of Transfusion Medicine, Nagoya University Hospital, 65 Tsurumai, Showa, Nagoya 466-8550, Japan. E-mail kojiy{at}med.nagoya-u.ac.jp

Objective— Although some patients with limb ischemia have recently undergone therapeutic angiogenesis by cell transplantation, their angiogenic potential has not been well characterized. It is also important to evaluate endothelial progenitor cell (EPC) contents in different stem cell sources to choose the best material for therapeutic angiogenesis.

Methods and Results— We quantitated the mRNA expression of EPC-specific molecules (eg, Flk-1, Flt-1, CD133, VE-cadherin, etc) in bone marrow-derived or peripheral blood-derived mononuclear cells obtained from patients with ischemic limbs, using real-time reverse-transcription polymerase chain reaction technique. The mRNA expression level of EPC markers was significantly lower in the patients than in healthy controls, which was consistent with results of flow cytometric analysis. However, the implantation of autologous bone marrow mononuclear cells increased the circulating EPCs in the peripheral blood of patients. We furthermore revealed the different expression pattern of EPC markers in possible sources for stem cell transplantation, including normal bone marrow, peripheral blood obtained from recombinant granulocyte colony–stimulating factor-treated donor, and umbilical cord blood.

Conclusions— Patients with peripheral obstructive arterial diseases may have lower angiogenic potential because of decreased expression of EPC specific molecules in their marrow and blood. Therapeutic angiogenesis by transplantation of autologous marrow mononuclear cells increased circulating EPCs in the patients and improved ischemic symptoms. (Arterioscler Thromb Vasc Biol. 2004;24:e192–e196.)

The gene expression of EPC-specific molecules in bone marrow-derived and peripheral blood-derived mononuclear cells, analyzed by real-time RT-PCR, was lower in patients with ischemic limbs than in healthy subjects. Therapeutic angiogenesis by autologous stem cell transplantation was effective for the patients and increased circulating EPCs.

Key Words: angiogenesis • stem cell • endothelial progenitor cells • transplantation • ischemia

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