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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:61.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Implantation of Adipose-Derived Regenerative Cells Enhances Ischemia-Induced Angiogenesis

Kazuhisa Kondo; Satoshi Shintani; Rei Shibata; Hisashi Murakami; Ryuichiro Murakami; Masayasu Imaizumi; Yasuo Kitagawa; Toyoaki Murohara

From the Department of Cardiology (K.K., S.S., R.S., H.M., R.M., T.M.), Nagoya University Graduate School of Medicine, and the Department of Bioengineering Sciences (M.I., Y.K.), Nagoya University Graduated School of Bioagricultural Sciences, Nagoya, Japan.

Correspondence to Toyoaki Murohara, MD, PhD, or Satoshi Shintani, MD, PhD, Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-8550 Japan. E-mail murohara{at}med.nagoya-u.ac.jp or shintani@med.nagoya-u.ac.jp.

Objective— Therapeutic angiogenesis using autologous stem/progenitor cells represents a novel strategy for severe ischemic diseases. Recent reports indicated that adipose tissues could supply adipose-derived regenerative cells (ADRCs). Accordingly, we examined whether implantation of ADRCs would augment ischemia-induced angiogenesis.

Method and Results— Adipose tissue was obtained from C57BL/6J mice, and ADRCs were isolated using standard methods. ADRCs expressed stromal cell–derived factor 1 (SDF-1) mRNA and proteins. Hind limb ischemia was induced and culture-expanded ADRCs, PBS, or mature adipocytes (MAs) as control cells were injected into the ischemic muscles. At 3 weeks, the ADRC group had a greater laser Doppler blood perfusion index and a higher capillary density compared to the controls. Implantation of ADRCs increased circulating endothelial progenitor cells (EPCs). SDF-1 mRNA abundance at ischemic tissues and serum SDF-1 levels were greater in the ADRC group than in the control group. Finally, intraperitoneal injection of an anti–SDF-1 neutralizing antibody reduced the number of circulating EPCs and therapeutic efficacies of ADRCs.

Conclusions— Adipose tissue would be a valuable source for cell-based therapeutic angiogenesis. Moreover, chemokine SDF-1 may play a pivotal role in the ADRCs-mediated angiogenesis at least in part by facilitating mobilization of EPCs.

Key Words: angiogenesis • adipose-derived regenerative cells • progenitor cells • chemokine

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