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First published online January 26, 2006
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2005-0349v1
24/5/1194    most recent
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Submitted on July 29, 2005
Accepted on January 17, 2006

Translational and Clinical Research

Angiogenesis facilitated by autologous whole bone marrow stem cell transplantation for Buerger's disease

Dong-Ik Kim 1*, Mi-Jung Kim 2, Jin-Hyun Joh 1, Sung-Wook Shin 3, Young-Soo Do 3, Ji-Young Moon 1, Na-Ri Kim 1, Joung-Eun Lim 4, Ae-Kyeong Kim 4, Hyun-Seon Eo 4, Byung-Soo Kim 5, Seung-Woo Cho 6, Seung-Hye Yang 2, Chan-Jeoung Park 2, Jong-Sup Shim 7

1 Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon, Korea
2 Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Institute for Life Sciences, Seoul, Korea
3 Department of Radiology, Surgery Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon, Korea
4 Samsung Biomedical Research Institute, Seoul, Korea
5 Department of Bioengineering, Hanyang University, Seoul, Korea
6 School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea
7 Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon, Korea

* To whom correspondence should be addressed. E-mail: dikim{at}smc.samsung.co.kr.


   Abstract

Background: We hypothesized that angiogenesis can be triggered by autologous whole bone marrow stem cell (BMSC) transplantation.

Methods and Results: 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 2.5mm diameter screw under fluoroscopic guidance. Clinical status and outcome were determined using the "Recommended Standards for Reports" (J Vasc Surg 1997). 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 75µg preoperatively. During the follow-up period (19.1 ± 3.5 months), 1 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), 5 limbs moderate (+2), and 9 limbs slight (+1) collateral development. However, 6 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 peripheral blood and in bone marrow after r-HuG-CSF injection.

Conclusions: 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.

Key Words. angiogenesis, bone marrow, stem cell




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