Autologous BoneMarrow Cell Transplantation for Treatment of Thromboangitis Obliterans_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Xuefeng ¹ , SHEN Zhenya ² , GU Yongquan ¹ , ZHANG Jian ¹ , YU Hengxi ¹ , GUO Lianrui ¹ , QI Lixing ¹ , CUI Shijun ¹ , WU Yingfeng ¹ , TONG Zhu ¹ , WANG Zhonggao ¹

1.Department of Vascular Surgery, Xuanwu Hospital, The Capital University of Medical Sciences, Beijing 100053, China;;
2.Department of Heart Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China;

Corresponding author：

Keywords：

Thromboangiitis obliterans; Autologous bone marrow-mononuclear cells; Skin ulcer; Ankle brachial index; Transcutaneous oxygen pressure

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Objective To investigate the effect and safety of autologous bone marrow-mononuclear cell (BM-MNC) transplantation on ischemic limb of patients with thromboangiitis obliterans (TAO).
Methods Thirteen patients with TAO underwent transplantation of autologous BM-MNC into ischemic muscles of 17 lower limbs. A series of subjective indexes (improvement of pain and cold sensation) and objective indexes including increase of ankle brachial index (ABI), transcutaneous oxygen pressure (TcPO2), and improvement of foot skin ulcer were used to evaluate the effects.
Results The outcomes were evaluated after 2 months of transplantation. The pain relief and improvement of cold feeling were in 15 limbs and 16 limbs, respectively. Before transplantation and 2 months after transplantation, ABI was 0.37±0.06 and 0.50±0.17, respectively (P lt;0.05), and TcPO2 of the ischemic legs were (24.59±3.36) mm Hg (1 mm Hg=0.133 kPa) and (35.00±10.44) mm Hg, respectively (P lt;0.05). ABI increased in 9 limbs. TcPO2 elevated in 14 limbs. Skin ulcer improved in 7 limbs. Thirteen patients were followed up from 4 to 18 months (average 8 months), the patients’ symptoms improved in 13 limbs. ABI was 0.45±0.14, which wasn’t different from those before transplantation and 2 months after transplantation (P gt;0.05). TcPO2 was (33.24±10.43) mm Hg, which was different from those before transplantation and 2 months after transplantation (P lt;0.05) and was elevated in 12 limbs. Skin ulcer healing was in 5 limbs. The ischemic symptoms in 2 patients were not relieved. There was no mortality and high level amputation. The following complications, such as proliferative retinopathy, malignant tumor, myocardial infarction, stroke or hemangioma, were not found in all patients.
Conclusion In patients with TAO, intramuscular transplantation of autologous BMMNC is a safe and effective method, and may improve symptoms and accelerate the healing of skin ulcer.

Citation： LI Xuefeng ,SHEN Zhenya,GU Yongquan,ZHANG Jian,YU Hengxi,GUO Lianrui,QI Lixing,CUI Shijun,WU Yingfeng,TONG Zhu,WANG Zhonggao. Autologous BoneMarrow Cell Transplantation for Treatment of Thromboangitis Obliterans. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(7): 656-659. doi: Copy

1.	Fontaine R, Buck P, Riveaux R, et al. Treatment of arterial obliterations; respective value of thrombectomies and thromboendarteriectomies, of arteriovenous shunts, and of vascular grafts (fresh venous autografts) [J]. Lyon Chir, 1951; 46(1): 7394.
2.	Sasaki S, Sakuma M, Yasuda K. Current status of thromboangiitis obliterans (Buerger’s disease) in Japan [J]. Int J Cardiol, 2000; 75 Suppl 1: S175S181.
3.	谷涌泉, 张建, 苏力, 等. 自体外周血单个核细胞移植治疗下肢缺血53例的临床研究 [J]. 中华普通外科杂志, 2006; 21(12): 848851.
4.	郭连瑞, 谷涌泉, 张建, 等. 自体骨髓干细胞移植治疗糖尿病足13例报告 [J]. 中华糖尿病杂志, 2004; 12(5): 313316.
5.	Saito Y, Sasaki K, Katsuda Y, et al. Effect of autologous bonemarrow cell transplantation on ischemic ulcer in patients with Buerger’s disease [J]. Circ J, 2007; 71(8): 11871192.
6.	Von Winiwater F. Ueber eine eigenthumliche from von endarteritis und endophlephitis mit gangran des fusses [J]. Arch Klin Chir, 1879; 23: 202226.
7.	Buerger L. Thromboangiitis obliterans: a study of the vascular lesions leading to presenile spontaneous gangrene [J]. Am J Med Sci, 1908; 136: 567580.
8.	Olin JW. Thromboangiitis obliterans (Buerger’s disease) [J]. N Engl J Med, 2000; 343(6): 864869.
9.	Olin JW, Young JR, Graor RA, et al. The changing clinical spectrum of thromboangiitis obliterans (Buerger’s disease) [J]. Circulation, 1990; 82(5 Suppl): Ⅳ3Ⅳ8.
10.	Ohta T, Ishioashi H, Hosaka M, et al. Clinical and social consequences of Buerger disease [J]. J Vasc Surg, 2004; 39(1): 176180.
11.	Bozkurt AK, Koksal C, Ercan M. The altered hemorheologic parameters in thromboangiitis obliterans: a new insight [J]. Clin Appl Thromb Hemost, 2004; 10(1): 4550.
12.	王雷, 辛世杰. 血栓闭塞性脉管炎的诊疗现状 [J]. 国际外科学杂志, 2007; 34(12): 834837.
13.	Isner JM, Asahara T. Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization [J]. J Clin Invest, 1999; 103(9): 12311236.
14.	TateishiYuyama E, Matsubara H, Murohara T, et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bonemarrow cells: a pilot study and a randomized controlled trial [J]. Lancet, 2002; 360(9331): 427435.
15.	谷涌泉, 郭连瑞, 张建, 等. 自体骨髓干细胞移植改善下肢严重缺血致运动功能障碍: 15例报告 [J]. 中国临床康复, 2004; 8(20): 39173919, i001.
16.	谷涌泉, 张建, 齐立行, 等. 自体骨髓干细胞移植治疗慢性下肢缺血94例不同病变分期患者的效果比较 [J]. 中国临床康复, 2005; 9(38): 710, i0001.
17.	Yamamoto K, Kondo T, Suzuki S, et al. Molecular evaluation of endothelial progenitor cells in patients with ischemic limbs: therapeutic effect by stem cell transplantation [J]. Arterioscler Thromb Vasc Biol, 2004; 24(12): e192e196.
18.	KajiguchiM, Kondo T, Izawa H, et al. Safety and efficacy of autologous progenitor cell transplantation for therapeutic angiogenesis in patients with critical limb ischemia [J]. Circ J, 2007; 71(2): 196201.
19.	Matoba S, Tatsumi T, Murohara T, et al. Longterm clinical outcome after intramuscular implantation of bone marrow mononuclear cells 〔Therapeutic Angiogenesis by Cell Transplantation (TACT) trial〕 in patients with chronic limb ischemia [J]. Am Heart J, 2008; 156(5): 10101018.
20.	杨镛, 陆平, 何晓明, 等. 人自体干细胞移植在重症肢体缺血血流重建中的疗效与评价 [J]. 中国普外基础与临床杂志, 2009; 16(2): 115118.
21.	杨国凯, 杨镛, 何晓明, 等. 外周血干细胞移植治疗血栓闭塞性脉管炎 [J]. 中国微创外科杂志, 2009; 9(9): 851852.
22.	缪健航, 师天雄, 胡锡祥, 等. 自体外周血干细胞移植治疗下肢动脉缺血性疾病的临床应用 [J]. 中国普外基础与临床杂志, 2008; 15(2): 106108.
23.	谷涌泉. 自体干细胞移植治疗下肢缺血性疾病的问题和对策 [J]. 外科理论与实践, 2009; 14(3): 269270.
24.	谷涌泉, 齐立行, 张建, 等. 自体骨髓单个核细胞移植治疗下肢缺血的中期疗效 [J]. 中国修复重建外科杂志, 2009; 23(3): 341344.

1. Fontaine R, Buck P, Riveaux R, et al. Treatment of arterial obliterations; respective value of thrombectomies and thromboendarteriectomies, of arteriovenous shunts, and of vascular grafts (fresh venous autografts) [J]. Lyon Chir, 1951; 46(1): 7394.
2. Sasaki S, Sakuma M, Yasuda K. Current status of thromboangiitis obliterans (Buerger’s disease) in Japan [J]. Int J Cardiol, 2000; 75 Suppl 1: S175S181.
3. 谷涌泉, 张建, 苏力, 等. 自体外周血单个核细胞移植治疗下肢缺血53例的临床研究 [J]. 中华普通外科杂志, 2006; 21(12): 848851.
4. 郭连瑞, 谷涌泉, 张建, 等. 自体骨髓干细胞移植治疗糖尿病足13例报告 [J]. 中华糖尿病杂志, 2004; 12(5): 313316.
5. Saito Y, Sasaki K, Katsuda Y, et al. Effect of autologous bonemarrow cell transplantation on ischemic ulcer in patients with Buerger’s disease [J]. Circ J, 2007; 71(8): 11871192.
6. Von Winiwater F. Ueber eine eigenthumliche from von endarteritis und endophlephitis mit gangran des fusses [J]. Arch Klin Chir, 1879; 23: 202226.
7. Buerger L. Thromboangiitis obliterans: a study of the vascular lesions leading to presenile spontaneous gangrene [J]. Am J Med Sci, 1908; 136: 567580.
8. Olin JW. Thromboangiitis obliterans (Buerger’s disease) [J]. N Engl J Med, 2000; 343(6): 864869.
9. Olin JW, Young JR, Graor RA, et al. The changing clinical spectrum of thromboangiitis obliterans (Buerger’s disease) [J]. Circulation, 1990; 82(5 Suppl): Ⅳ3Ⅳ8.
10. Ohta T, Ishioashi H, Hosaka M, et al. Clinical and social consequences of Buerger disease [J]. J Vasc Surg, 2004; 39(1): 176180.
11. Bozkurt AK, Koksal C, Ercan M. The altered hemorheologic parameters in thromboangiitis obliterans: a new insight [J]. Clin Appl Thromb Hemost, 2004; 10(1): 4550.
12. 王雷, 辛世杰. 血栓闭塞性脉管炎的诊疗现状 [J]. 国际外科学杂志, 2007; 34(12): 834837.
13. Isner JM, Asahara T. Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization [J]. J Clin Invest, 1999; 103(9): 12311236.
14. TateishiYuyama E, Matsubara H, Murohara T, et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bonemarrow cells: a pilot study and a randomized controlled trial [J]. Lancet, 2002; 360(9331): 427435.
15. 谷涌泉, 郭连瑞, 张建, 等. 自体骨髓干细胞移植改善下肢严重缺血致运动功能障碍: 15例报告 [J]. 中国临床康复, 2004; 8(20): 39173919, i001.
16. 谷涌泉, 张建, 齐立行, 等. 自体骨髓干细胞移植治疗慢性下肢缺血94例不同病变分期患者的效果比较 [J]. 中国临床康复, 2005; 9(38): 710, i0001.
17. Yamamoto K, Kondo T, Suzuki S, et al. Molecular evaluation of endothelial progenitor cells in patients with ischemic limbs: therapeutic effect by stem cell transplantation [J]. Arterioscler Thromb Vasc Biol, 2004; 24(12): e192e196.
18. KajiguchiM, Kondo T, Izawa H, et al. Safety and efficacy of autologous progenitor cell transplantation for therapeutic angiogenesis in patients with critical limb ischemia [J]. Circ J, 2007; 71(2): 196201.
19. Matoba S, Tatsumi T, Murohara T, et al. Longterm clinical outcome after intramuscular implantation of bone marrow mononuclear cells 〔Therapeutic Angiogenesis by Cell Transplantation (TACT) trial〕 in patients with chronic limb ischemia [J]. Am Heart J, 2008; 156(5): 10101018.
20. 杨镛, 陆平, 何晓明, 等. 人自体干细胞移植在重症肢体缺血血流重建中的疗效与评价 [J]. 中国普外基础与临床杂志, 2009; 16(2): 115118.
21. 杨国凯, 杨镛, 何晓明, 等. 外周血干细胞移植治疗血栓闭塞性脉管炎 [J]. 中国微创外科杂志, 2009; 9(9): 851852.
22. 缪健航, 师天雄, 胡锡祥, 等. 自体外周血干细胞移植治疗下肢动脉缺血性疾病的临床应用 [J]. 中国普外基础与临床杂志, 2008; 15(2): 106108.
23. 谷涌泉. 自体干细胞移植治疗下肢缺血性疾病的问题和对策 [J]. 外科理论与实践, 2009; 14(3): 269270.
24. 谷涌泉, 齐立行, 张建, 等. 自体骨髓单个核细胞移植治疗下肢缺血的中期疗效 [J]. 中国修复重建外科杂志, 2009; 23(3): 341344.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Autologous BoneMarrow Cell Transplantation for Treatment of Thromboangitis Obliterans

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