Division of Cardiology, Department of Internal Medicine, Pusan National University, Medical Research Institute, Pusan Medical University Hospital, Busan, Korea.
Circ J. 2012;76(7):1750-60. doi: 10.1253/circj.cj-11-1135. Epub 2012 Apr 12.
Treatment of critical limb ischemia (CLI) by bypass operation or percutaneous vascular intervention is occasionally difficult. The safety and efficacy of multiple intramuscular adipose tissue-derived mesenchymal stem cells (ATMSC) injections in CLI patients was determined in the study.
The study included 15 male CLI patients with ischemic resting pain in 1 limb with/without non-healing ulcers and necrotic foot. ATMSC were isolated from adipose tissue of thromboangiitis obliterans (TAO) patients (B-ATMSC), diabetes patients (D-ATMSC), and healthy donors (control ATMSC). In a colony-forming unit assay, the stromal vascular fraction of TAO and diabetic patients yielded lesser colonies than that of healthy donors. D-ATMSC showed lower proliferation abilitythan B-ATMSC and control ATMSC, but they showed similar angiogenic factor expression with control ATMSC and B-ATMSC. Multiple intramuscular ATMSC injections cause no complications during the follow-up period (mean follow-up time: 6 months). Clinical improvement occurred in 66.7% of patients. Five patients required minor amputation during follow-up, and all amputation sites healed completely. At 6 months, significant improvement was noted on pain rating scales and in claudication walking distance. Digital subtraction angiography before and 6 months after ATMSC implantation showed formation of numerous vascular collateral networks across affected arteries.
Multiple intramuscular ATMSC injections might be a safe alternative to achieve therapeutic angiogenesis in patients with CLI who are refractory to other treatment modalities.
旁路手术或经皮血管介入治疗严重肢体缺血（CLI）偶尔会有困难。本研究旨在确定多次肌肉内脂肪组织源性间充质干细胞（ATMSC）注射治疗 CLI 患者的安全性和有效性。
该研究纳入了 15 名男性 CLI 患者，这些患者单肢存在缺血性静息痛，伴有/不伴有未愈合的溃疡和坏死性足部。ATMSC 从血栓闭塞性脉管炎（TAO）患者（B-ATMSC）、糖尿病患者（D-ATMSC）和健康供体（对照 ATMSC）的脂肪组织中分离得到。在集落形成单位测定中，TAO 和糖尿病患者的基质血管部分比健康供体产生的集落更少。D-ATMSC 的增殖能力低于 B-ATMSC 和对照 ATMSC，但它们与对照 ATMSC 和 B-ATMSC 具有相似的血管生成因子表达。在随访期间（平均随访时间：6 个月），多次肌肉内 ATMSC 注射未引起任何并发症。66.7%的患者出现临床改善。5 例患者在随访期间需要进行小截肢，所有截肢部位均完全愈合。在 6 个月时，疼痛评分量表和跛行行走距离均有显著改善。ATMSC 植入前后的数字减影血管造影显示，受累动脉之间形成了许多血管侧支网络。
多次肌肉内 ATMSC 注射可能是治疗其他治疗方法无效的 CLI 患者的一种安全的治疗选择，可以实现治疗性血管生成。
