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European Heart Journal Advance Access published online on April 26, 2005
European Heart Journal, doi:10.1093/eurheartj/ehi285
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European Heart Journal © The European Society of Cardiology 2005; all rights reserved
Received August 17, 2004
Revised March 8, 2005
Accepted March 24, 2005

Clinical research

Therapeutical potential of blood-derived progenitor cells in patients with peripheral arterial occlusive disease and critical limb ischaemia

Karsten Lenk 1, Volker Adams 1, Philipp Lurz 1, Sandra Erbs 1, A. Linke 1, Stephan Gielen 1, Andrej Schmidt 2, Dierck Scheinert 2, Giancarlo Biamino 2, Frank Emmrich 3, Gerhard Schuler 1, and Rainer Hambrecht 1*

1 Department of Cardiology, University of Leipzig Heart Center, Strümpellstrasse 39, D-04289 Leipzig, Germany
2 Department of Angiology, University of Leipzig Heart Center, Strümpellstrasse 39, D-04289 Leipzig, Germany
3 Institute of Clinical Immunology and Transfusion Medicine, Leipzig, Germany

* To whom correspondence should be addressed.
Rainer Hambrecht, E-mail: hamr{at}medizin.uni-leipzig.de


  Abstract

Aims Despite considerable advances in the therapy of patients with peripheral arterial occlusive disease (PAOD) and critical limb ischaemia (CLI), a substantial number remain, in whom amputation has to be considered the only and final option. Recent evidence from animal models of hind limb ischaemia suggests that neovascularization induced by circulating blood-derived progenitor cells (CPCs) may permit limb salvage. It remains unclear, however, whether an intra-arterial application of autologous CPCs in patients with infrapopliteal PAOD and CLI is safe, feasible, and of potentially beneficial effects.

Methods and results Seven patients with critical PAOD were treated with an intra-arterial infusion of autologous CPCs (39 ± 24x106) isolated from peripheral blood. Pre-interventional stimulation with G-CSF and CPC application was well tolerated. Twelve weeks after CPC administration, the pain-free walking distance increased from 6 ± 13 to 195 ± 196 m. A significant increase in the ankle-brachial index, transcutaneous O2, flow-dependent vasodilation, flow reserve in response to adenosine, and endothelium-dependent vasodilation was observed.

Conclusion These preliminary data in a small series of patients with CLI without surgical or interventional options indicate that CPC application is safe, feasible, and may improve both functional and clinical indices.

Keywords: Circulating progenitor cells; Angiogenesis; Critical limb ischaemia; Neovascularization; Peripheral arterial occlusive disease.
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