Jonsson T B, Larzon T, Arfvidsson B, Tidefelt U, Axelsson C G, Jurstrand M, Norgren L
Department of Surgery, University Hospital, Örebro, Sweden.
Int Angiol. 2012 Feb;31(1):77-84.
Trials have reported clinical improvement and reduced need for amputation in critical limb ischemia (CLI) patients receiving therapeutic angiogenesis with stem cells. Our objective was to test peripheral stem cell therapy efficacy and safety to gain experiences for further work.
We included nine CLI patients (mean age 76.7 ±9.7). Stem cells were mobilized to the peripheral blood by administration of G-CSF (Filgrastim) for 4 days, and were collected on day five, when 30 mL of a stem cell suspension was injected into 40 points of the limb. The clinical efficacy was evaluated by assessing pain relief, wound healing and changes in ankle-brachial pressure index (ABI). Local metabolic and inflammatory changes were measured with microdialysis, growth factors and cytokine level determination. Patients were followed for 24 weeks.
Four patients experienced some degree of improvement with pain relief and/or improved wound healing and ABI increase. One patient was lost to follow up due to chronic psychiatric illness; one was amputated after two weeks. Two patients had a myocardial infarction (MI), one died. One patient died from a massive mesenteric thrombosis after two weeks and one died from heart failure at week 11. Improved patients showed variable effects in cytokine-, growth factor- and local metabolic response.
Even with some improvement in four patients, severe complications in four out of nine patients, and two in relation to the bone marrow stimulation, made us terminate the study prematurely. We conclude that with the increased risk and the reduced potential of the treatment, peripheral blood stem cell treatment in the older age group is less appropriate. Metabolic and inflammatory response may be of value to gain insight into mechanisms and possibly to evaluate effects of therapeutic angiogenesis.
试验报告称，接受干细胞治疗性血管生成的严重肢体缺血（CLI）患者临床症状有所改善，截肢需求减少。我们的目标是测试外周干细胞治疗的疗效和安全性，为进一步研究积累经验。
我们纳入了9例CLI患者（平均年龄76.7±9.7岁）。通过给予粒细胞集落刺激因子（非格司亭）4天，将干细胞动员至外周血，在第5天采集，此时将30 mL干细胞悬液注射到肢体的40个部位。通过评估疼痛缓解情况、伤口愈合情况和踝肱压力指数（ABI）的变化来评估临床疗效。用微透析、生长因子和细胞因子水平测定来测量局部代谢和炎症变化。对患者进行了24周的随访。
4例患者在疼痛缓解和/或伤口愈合改善以及ABI增加方面有一定程度的改善。1例患者因慢性精神疾病失访；1例在两周后接受了截肢手术。2例患者发生心肌梗死（MI），1例死亡。1例患者在两周后死于大面积肠系膜血栓形成，1例在第11周死于心力衰竭。症状改善的患者在细胞因子、生长因子和局部代谢反应方面表现出不同的效果。
尽管有4例患者有所改善，但9例患者中有4例出现严重并发症，其中2例与骨髓刺激有关，这使我们提前终止了研究。我们得出结论，随着治疗风险的增加和潜力的降低，老年组外周血干细胞治疗不太合适。代谢和炎症反应可能有助于深入了解机制，并可能评估治疗性血管生成的效果。
