Therapeutic angiogenesis in patients with severe limb ischemia by transplantation of a combination stem cell product
Therapeutic angiogenesis in patients with severe limb ischemia by transplantation of a combination stem cell product
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DOI：
10.1016/j.jtcvs.2011.08.053
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发表时间：
2012-08-01
影响因子：
6
通讯作者：
Minguell, Jose J.
中科院分区：
文献类型：
--
作者：
Lasala, Gabriel P.;Silva, Jose A.;Minguell, Jose J.
目的：血管生成涉及内皮祖细胞、周细胞、生长因子和细胞基质成分的相互作用。间充质干细胞与周细胞关系密切，能产生多种血管生长因子和基质分子，是一种很有前途的治疗方法。我们推测，联合使用细胞产品(间充质干细胞和内皮祖细胞的来源)是安全和有效的，并且可能优化单独使用内皮祖细胞所获得的临床结果。这项研究评估了联合细胞产物肌肉内输注是否是改善严重缺血肢体血流灌注的一种可行、有效和持久的治疗方式。方法：肢体缺血患者(n=26)在缺血最严重的小腿肌肉内(腓肠肌)输注联合细胞产物，在(缺血较少的)对侧小腿注射安慰剂产品。临床随访(输液后0.5个月、1个月、2个月和4个月)包括评估无痛步行时间、踝臂指数、核素显像和生活质量调查。疗效评价显示，细胞输注后行走时间和踝臂指数均有明显改善。此外，~(99m)m-四氧嘧啶核素骨显像显示，治疗侧肢体血流灌注较对照侧明显增加。结论：本II期临床试验表明，联合应用细胞疗法能安全有效地增加肢体缺血患者缺血肢体的血流量。(《胸心外科杂志》2012；144：377-82)
Objective: Angiogenesis involves the interplay of endothelial progenitor cells, pericytes, growth factors, and cellular matrix components. The use of mesenchymal stem cells, which are closely related to pericytes and produce diverse angiogenic growth factors and matrix molecules, seems to be a promising therapeutic modality. We postulate that the use of a combination cell product (mesenchymal stem cells in conjunction with a source of endothelial progenitor cells) is safe and efficient and may optimize the clinical results obtained with the use of endothelial progenitor cells alone. This study assessed whether the intramuscular infusion of a combination cell product represents a viable, effective, and lasting therapeutic modality to improve perfusion in severely ischemic limbs.Methods: Patients with limb ischemia (n = 26) received an intramuscular (gastrocnemius) infusion of the combination cell product in the most ischemic leg and a placebo product in the (less ischemic) contralateral leg. Clinical follow-up (months 0.5, 1, 2, and 4 postinfusion) included evaluation of pain-free walking time, ankle-brachial index, perfusion scintigraphy, and quality of life survey.Results: No adverse events occurred after infusion. Efficacy assessment indicated that after cell infusion there was a significant improvement in walking time and ankle-brachial index. In addition, technetium-99m-tetrofosmin scintigraphy demonstrated a significant increase of perfusion in the treated limbs compared with the respective control legs.Conclusions: This phase II clinical trial shows that the use of a combination cell therapy is safe and effective in increasing blood flow in the ischemic legs of patients with limb ischemia. (J Thorac Cardiovasc Surg 2012;144:377-82)