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TRANSLATIONAL AND CLINICAL RESEARCH

Angiogenesis Facilitated by Autologous Whole Bone Marrow Stem Cell Transplantation for Buerger’s Disease

^a Division of Vascular Surgery and
^b Departments of Radiology and
^c Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea;
^d Department of Laboratory Medicine, University of Ulsan College of Medicine, Asan Institute for Life Sciences, Seoul, Korea;
^e Department of Bioengineering, Hanyang University, Seoul, Korea;
^f Samsung Biomedical Research Institute,
^g School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea

Key Words. Angiogenesis • Bone marrow • Stem cells

Correspondence: Dong-Ik Kim, M.D., Ph.D., Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwondong, Kangnamku, Seoul 135-710, Korea. Telephone: 82-2-3410-3467; Fax: 82-2-3410-0040; e-mail: dikim{at}smc.samsung.co.kr or Mi-Jung Kim, Department of Laboratory Medicine, University of Ulsan College of Medicine, Asan Institute for Life Sciences, 388 Pungnap-2 dong, Songpa-gu, Seoul 138-736, Korea. Telephone: 82-2-3010-4147; Fax: 82-2-3010-4182; E-mail: mijkim{at}amc.seoul.kr

Received July 29, 2005; accepted for publication January 17, 2006.
We hypothesized that angiogenesis can be triggered by autologous whole bone marrow stem cell transplantation. Twenty-seven patients (34 lower limbs) with Buerger’s disease, who were not candidates for surgical revascularization or radiologic intervention, were enrolled in this study. Six sites of the tibia bone were fenestrated using a 2.5-mm-diameter screw under fluoroscopic guidance. Clinical status and outcome were determined using the "Recommended Standards for Reports." To mobilize endothelial progenitor cells (EPCs) from bone marrow, recombinant human granulocyte colony-stimulating factor (r-HuG-CSF) was injected subcutaneously as a dose of 75 µg, preoperatively. During the follow-up period (19.1 ± 3.5 months), one limb showed a markedly improved outcome (+3), and 26 limbs showed a moderately improved outcome (+2). Thirteen limbs among 17 limbs with nonhealing ulcers healed. Postoperative angiograms were obtained for 22 limbs. Two limbs showed marked (+3), five limbs moderate (+2), and nine limbs slight (+1) collateral development. However, six limbs showed no collateral development (0). Peripheral blood and bone marrow samples were analyzed for CD34 and CD133 molecules to enumerate potential EPCs, and EPC numbers were found to be increased in peripheral blood and in bone marrow after r-HuG-CSF injection. In conclusion, the transplantation of autologous whole BMCs by fenestration of the tibia bone represents a simple, safe, and effective means of inducing therapeutic angiogenesis in patients with Buerger’s disease.

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