Therapeutic angiogenesis by autologous bone marrow cell implantation for refractory chronic peripheral arterial disease using assessment of neovascularization by 99mTc-tetrofosmin (TF) perfusion scintigraphy
Therapeutic angiogenesis by autologous bone marrow cell implantation for refractory chronic peripheral arterial disease using assessment of neovascularization by 99mTc-tetrofosmin (TF) perfusion scintigraphy
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DOI：
10.3727/000000004783983837
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发表时间：
2004-01-01
影响因子：
3.3
通讯作者：
Takano, T
中科院分区：
文献类型：
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作者：
Miyamoto, M;Yasutake, M;Takano, T
本研究采用tc -99m-四氟磷（TF）灌注显像目视和定量分析的方法，探讨了自体骨髓单个核细胞加血小板（包括内皮祖细胞（EPCs））移植治疗难治性慢性外周动脉疾病（PAD）的疗效和安全性，并对各种定量评价进行了客观研究。我们在本试验中连续行12例，19例四肢和手部重度慢性PAD，几乎为Fontaine IV级（11/12例，约92%）。这种治疗对于缓解PAD的剧烈疼痛非常有效，特别是对于伯格氏病。我们采用视觉模拟量表（VAS）测量疼痛程度。植入前最大疼痛水平为66.5 +/- 5.0 mm，植入后最大疼痛水平为12.1 +/- 2.2 mm （p < 0.001）。11例（11/12例，92%）腿部和手指静息性疼痛得到缓解。所有患者均可在跑步机上测量无痛步行时间，明显改善（植入前140 +/- 53 s vs植入后451 +/- 74 s， p = 0.034）。骨髓单个核细胞植入组的静息踝肱压力指数（ABI）也明显改善（植入前0.65 +/- 0.08，植入后0.73 +/- 0.07,p = 0.055）。Tc-99m-TF灌注显像显示，植入前近端区域（膝关节至踝关节区域）为1.32 +/- 0.10，植入后为1.56 +/- 0.11 （p = 0.007）。远端Tc-99m-TF灌注显像（踝关节至趾端或腕关节至指端），植入前为0.79 +/- 0.06，植入后为0.83 +/- 0.06 （p = 0.29）。缺血的腿部和手部注射后，血流灌注增加。Tc-99m-TF灌注显像可有效评估新生血管中侧支血管的视觉和定量分析。我们成功地用这种新疗法治疗了最严重的慢性外周动脉疾病，目前的任何治疗方法都无法治愈。因此，这种治疗性血管生成可能是挽救严重缺血肢体和手部的新策略。
We investigated efficacy and safety of implantation of autologous bone marrow mononuclear cells plus platelets, including endothelial progenitor cells (EPCs), for recovering refractory chronic peripheral arterial disease (PAD) using visual and quantitative analyses by Tc-99m-tetrofosmin (TF) perfusion scintigraphy, and also investigated various quantitative assessments objectively. We performed 12 consecutive cases and 19 limbs and hands with severe chronic PAD that were almost Fontaine class IV (11/12 cases, about 92%) in this trial. This treatment was very effective in relieving severe pain of PAD, especially for Buerger's disease. We used a visual analog scale (VAS) for measurement of pain level. The maximum pain level before implantation was 66.5 +/- 5.0 mm, and it decreased to 12.1 +/- 2.2 mm after implantation (p < 0.001). Rest pain in legs and fingers was resolved in 11 cases (11/12 cases, 92%). All patients could measure pain-free walking time on a treadmill, which improved remarkably (140 +/- 53 s before implantation vs. 451 +/- 74 s after implantation, p = 0.034). Resting ankle brachial pressure index (ABI) in legs implanted with bone marrow mononuclear cells was also improved (0.65 +/- 0.08 before implantation vs. 0.73 +/- 0.07 after implantation, p = 0.055). According to Tc-99m-TF perfusion scintigraphy, the proximal area (region from knee to ankle) was 1.32 +/- 0.10 before implantation versus 1.56 +/- 0.11 after implantation (p = 0.007). Tc-99m-TF perfusion scintigraphy in the distal area (region from ankle to end of toes, or from wrist to end of fingers) was 0.79 +/- 0.06 before implantation versus 0.83 +/- 0.06 after implantation (p = 0.29). Ischemic legs and hands that were injected showed increased perfusion blood flow. Tc-99m-TF perfusion scintigraphy was effective to estimate visual and quantitative analysis of collateral vessels in neovascularization. We were successful with this new treatment for the most severe, chronic PAD that was not curable by any of the current treatments. Thus, this therapeutic angiogenesis could be a new strategy for saving severe ischemic limbs and hands.