?The age-adjusted prevalence of peripheral arterial disease (PAD) in the U.S. population has been estimated to approach 12%. The clinical consequences of occlusive PAD include pain on walking (claudication), pain at rest, and loss of tissue integrity in the distal limbs;the latter may ultimately lead to amputation of a portion of the lower extremity. Surgical bypass techniques and percutaneous catheter-based interventions may be used to successfully revascularize the limbs of certain patients with PAD. In many patients, however, the anatomic extent and distribution of arterial occlusion is too severe to permit relief of pain and/or healing of ischemic ulcers. No effective medical therapy is available for the treatment of such patients, for many of whom amputation represents the only hope for alleviation of symptoms. The ultimate failure of medical treatment and mechanical revascularization in significant numbers of patients has led to attempts to develop alternative therapies for ischemic disease. These strategies include administration of angiogenic cytokines, either as recombinant protein or as gene therapy, and more recently, to investigations of cell therapy. The concept that new blood vessel formation could be augmented by administering bone marrow cells or circulating endothelial progenitor cells (EPCs) is based upon work performed in our laboratory and others in the past 7 years. The purpose of this pilot clinical protocol is to investigate the efficacy and safety of intramuscular injection of autologously derived EPCs in patients with PAD as a means of augmenting blood vessel formation and perfusion. The rationale for this human protocol is based upon preclinical studies performed in our laboratory and detailed in this application. The completion of the proposed studies will provide data regarding the safety and efficacy of EPC therapy necessary for the design of larger randomized trials and will also provide valuable insights regarding treatment of ischemic disease with a cell based approach.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-CICS (01))
Program Officer
Tolunay, Eser
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Northwestern University at Chicago
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Morishita, Yoshihiro; Kobayashi, Koichi; Klyachko, Ekaterina et al. (2016) Wnt11 Gene Therapy with Adeno-associated Virus 9 Improves Recovery from Myocardial Infarction by Modulating the Inflammatory Response. Sci Rep 6:21705
Sekiguchi, Haruki; Ii, Masaaki; Jujo, Kentaro et al. (2013) Estradiol promotes neural stem cell differentiation into endothelial lineage and angiogenesis in injured peripheral nerve. Angiogenesis 16:45-58
Raval, Zankhana; Losordo, Douglas W (2013) Cell therapy of peripheral arterial disease: from experimental findings to clinical trials. Circ Res 112:1288-302
Mackie, Alexander R; Klyachko, Ekaterina; Thorne, Tina et al. (2012) Sonic hedgehog-modified human CD34+ cells preserve cardiac function after acute myocardial infarction. Circ Res 111:312-21
Fadini, Gian Paolo; Losordo, Douglas; Dimmeler, Stefanie (2012) Critical reevaluation of endothelial progenitor cell phenotypes for therapeutic and diagnostic use. Circ Res 110:624-37
Sekiguchi, Haruki; Ii, Masaaki; Jujo, Kentaro et al. (2012) Estradiol triggers sonic-hedgehog-induced angiogenesis during peripheral nerve regeneration by downregulating hedgehog-interacting protein. Lab Invest 92:532-42
Losordo, Douglas W; Kibbe, Melina R; Mendelsohn, Farrell et al. (2012) A randomized, controlled pilot study of autologous CD34+ cell therapy for critical limb ischemia. Circ Cardiovasc Interv 5:821-30
Nishimura, Yukihide; Ii, Masaaki; Qin, Gangjian et al. (2012) CXCR4 antagonist AMD3100 accelerates impaired wound healing in diabetic mice. J Invest Dermatol 132:711-20
Losordo, Douglas W; Henry, Timothy D; Davidson, Charles et al. (2011) Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circ Res 109:428-36
Tongers, Jörn; Losordo, Douglas W; Landmesser, Ulf (2011) Stem and progenitor cell-based therapy in ischaemic heart disease: promise, uncertainties, and challenges. Eur Heart J 32:1197-206

Showing the most recent 10 out of 49 publications