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Original Articles

Long-Term Outcome of Therapeutic Neovascularization Using Peripheral Blood Mononuclear Cells for Limb Ischemia

Junji Moriya, MD, PhD^*; Tohru Minamino, MD, PhD^*; Kaoru Tateno, MD, PhD^*; Naomi Shimizu, MD, PhD; Yoichi Kuwabara, MD, PhD; Yasunori Sato, PhD; Yasushi Saito, MD, PhD and Issei Komuro, MD, PhD

From the Departments of Cardiovascular Science and Medicine (J.M., T.M., K.T., Y.K., I.K.) and Clinical Cell Biology and Medicine (N.S., Y.S.), Chiba University Graduate School of Medicine, Chuo-Ku, Chiba, Japan; PRESTO (T.M.), Japan Science and Technology Agency, Saitama, Japan; and Clinical Research Center (Y.S.), Chiba University Hospital, Chuo-Ku, Chiba, Japan.

Correspondence to Issei Komuro, MD, PhD, Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba 260-8670, Japan. E-mail komuro-tky{at}umin.ac.jp

Received June 14, 2008; accepted March 18, 2009.

Background— Injection of bone marrow mononuclear cells has been reported to promote neovascularization of ischemic tissues effectively. We found that peripheral blood mononuclear cells were as efficient as bone marrow mononuclear cells for the treatment of limb ischemia in animals and showed that this treatment was feasible and safe in no-option patients with limb ischemia. However, the long-term outcome of such therapy has not been investigated.

Methods and Results— We retrospectively analyzed the data for 42 patients who were treated between July 2002 and December 2005 by using the log-rank test, the Kaplan-Meier method, and the Cox proportional hazard model. Improvement of ischemic symptoms was observed in 60% to 70% of the patients. The annual rate of major amputation was decreased markedly by treatment. Improvement of ischemic symptoms was less marked in arteriosclerosis obliterans (ASO) patients on dialysis compared with nonhemodialysis ASO or thromboangiitis obliterans patients. Indeed, the survival rate of these patients was lower than that of nonhemodialysis ASO or thromboangiitis obliterans patients. Major adverse events such as death, major amputation, and cardiovascular events occurred mostly in ASO patients, and most of them were on dialysis. There was no significant difference in the cardiovascular event-free rate between responders and nonresponders. The survival rate of younger responders was better than that of nonresponders.

Conclusions— Although this study was not placebo-controlled and these initial results were from a retrospective analysis, injection of peripheral blood mononuclear cells might be safe and potentially effective for the treatment of limb ischemia, but caution is needed when managing ASO patients on dialysis.

Key Words: angiogenesis • cell therapy • hemodialysis • peripheral vascular disease

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CLINICAL PERSPECTIVE

*Drs Moriya, Minamino, and Tateno contributed equally to this work.

The online-only Data Supplement is available at http://circinterventions.ahajournals.org/cgi/content/full/10.1161/CIRCINTERVENTIONS.108.799361/DC1.