Published Online
on March 30, 2009

A more recent version of this article appeared on June 1, 2009

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Original Article

Long-term outcome of therapeutic neovascularization using peripheral blood mononuclear cells for limb ischemia

Junji Moriya¹; Tohru Minamino²; Kaoru Tateno¹; Naomi Shimizu¹; Yoichi Kuwabara¹; Yasunori Sato³; Yasushi Saito³ and Issei Komuro^1,4

¹ Chiba University, Chiba, Japan;
² Chiba University, Chiba; and PRESTO, Japan Science and Technology Agency, Saitama, Japan;
³ Chiba University Hospital, Chiba, Japan

⁴ E-mail: komuro-tky{at}umin.ac.jp

Background—Injection of bone marrow mononuclear cells (BM-MNC) has been reported to effectively promote neovascularization of ischemic tissues. We found that peripheral blood-MNC were as efficient as BM-MNC 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 60-70% of the patients. The annual rate of major amputation was markedly decreased by treatment. Improvement of ischemic symptoms was less marked in arteriosclerosis obliterans (ASO) patients on dialysis compared with non-hemodialysis ASO or thromboangiitis obliterans (TAO) patients. Indeed, the survival rate of these patients was lower than that of non-hemodialysis ASO or TAO patients. Major adverse events such as death, major amputation, and cardiovascular events mostly occurred in ASO patients and most of them were on dialysis. There was no significant difference in the cardiovascular event-free rate between responders and non-responders. The survival rate of younger responders was better than that of non-responders.

Conclusions—Although this study was not placebo-controlled and these initial results were from a retrospective analysis, injection of PB-MNC 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 • peripheral vascular disease • cell therapy • hemodialysis

Author contributions: Drs Junji Moriya, Tohru Minamino, and Kaoru Tateno contributed equally to this work.