脐带华通胶间充质干细胞治疗缺血性心力衰竭的2年随访观察

Clinical efficacy of Wharton's jelly mesenchymal stem cell on ischemic heart failure: A 2-year follow-up study

目的观察人脐带华通胶间充质干细胞（Wharton＇s jelly mesenchymal stem cell,WJ-MSCs）经冠脉移植治疗缺血性心力衰竭的远期临床疗效和安全性。方法选择2010年12月-2013年12月于解放军总医院住院的缺血性心力衰竭并血运重建患者40例,随机分为移植组（20例）和对照组（20例）。制备人脐带华通胶间充质干细胞混悬液。两组均行冠状动脉造影,移植组经既往梗死相关动脉或心脏供血优势动脉注入10 ml干细胞悬液（细胞数2×10^7）,对照组经梗死相关动脉或心脏供血优势动脉注入10 ml 0.9%氯化钠注射液。治疗前、移植后6个月、12个月、18个月及24个月化验肝肾功能、肿瘤标记物及血浆脑钠肽（B-type natriuretic peptide,BNP）,同时行超声心动图测量左心室射血分数（left ventricular ejection fraction,LVEF）、左心室舒张末容量（left ventricle end-diastolic volume,LVEDV）,进行6 min步行试验（6-minute walk test,6MWT）及SF-36健康量表问卷调查以评估患者日常活动耐量及生活质量。统计24个月内心源性死亡、非致死性心肌梗死、血运重建、脑梗死及其他严重不良事件发生率。结果 12个月时与治疗前比较,移植组LVEF、6MWD增幅最大,而LVEDV、BNP下降幅度最大[（43.64±9.27）%vs（36.38±6.38）%,（316.7±68.5）m vs（227.2±57.4）m,（135.97±34.85）ml vs（174.45±55.16）ml,（2 434.8±1 963.8）pg/ml vs（4 571.8±3 125.8）pg/ml;P〈0.05];24个月时移植组LVEF、LVEDV、BNP与治疗前比较,差异均无统计学意义（P〉0.05）,6MWD较治疗前明显增加,差异有统计学意义（P〈0.05）。两组同期比较,移植组LVEF、6MWD、LVEDV、BNP均优于对照组（P〈0.05）。随访24个月中,移植组身体功能评分及总体健康评分与治疗前比较呈升高趋势（P〈0.05）;运动限制评分在6个月及12个月时与治疗前比较呈下降趋势（P〈0.05）。两组同期比较发现,移植组身体功能评分及总体健康评分均优于同期对照组（P〈0.05）。两组不良事件发生率差异无统计学意义（P〉0.05）,两组治疗前后血尿常规、肝肾功能、心肌酶、肿瘤标记物水平无统计学差异（P〉0.05）。结论 18个月内经冠状动脉移植WJ-MSCs可改善缺血性心衰患者左心室功能,减少左心室容量,阻止或延缓左心室重构,24个月时仍提高了患者活动耐量及生活质量,且安全有效。

Objective To evaluate the long-term clinical efficacy and safety of human umbilical cord Wharton＇s jelly mesenchymal stem cell（WJ-MSC） on ischemic heart failure（IHF）. Methods From December 2010 to December 2013, a total of 40 hospitalized ischemic heart failure patients who were successfully revascularized with drug-eluting stents were enrolled and randomly divided into two groups： WJ-MSCs group（n=20） and control group（n=20）. WJ-MSC（2×10^7） were prepared, and patients in both groups had undergone coronary arteriography. Then 10 ml of WJ-MSC（2×10^7） suspension was slowly injected via previous infarctrelated coronary artery or predominant blood supply artery for heart in WJ-MSCs group, while 10 ml of 0.9% sodium chloride was slowly injected via the same path of patients in control group. Hepatic and renal function parameters, tumor markers and B-type natriuretic peptide（BNP） plasma level were analyzed before and after 6, 12, 18, and 24 months of transplantation. Echocardiography was performed to measure left ventricular ejection fraction（LVEF） and left ventricle end-diastolic volume（LVEDV）. The quality of life and daily activity were evaluated by SF-36 health scale questionnaire and 6-minute walk test（6MWT）. The incidences of cardiac death, non-fatal myocardial infarction, revascularization, cerebral infarction and other serious adverse events were recorded during the follow-up of 24 months. Results Compared with before treatment, the LVEF and 6MWD in WJ-MSCs group increased to the highest level at 12 months after transplantation, while the LVEDV and BNP decreased significantly [（36.38±6.38）% vs（43.64±9.27）%,（227.2±57.4） m vs（316.7±68.5） m, P〈0.05;（174.45±55.16） ml vs（135.97±34.85） ml and（4 571.8±3 125.8）pg/ml vs（2 434.8±1 963.8） pg/ml, P〈0.05]. There was no significant difference in LVEF, LVEDV and BNP at 24 months after transplantation in WJ-MSCs group compared with before treatment（P〉0.05）, while the 6MWD increased significantly（P〈0.05）. Patients in WJ-MSCs group achieved better outcomes（LEVF, 6MWD, LVEDD and BNP） than control group during the same period（P〈0.05）. Compared with before treatment, the physical function and general health in WJ-MSCs group showed an increasing trend during the follow-up of 24 months（P〈0.05）; while the score of role limitation decreased at 6 months and 12 months after transplantation（P〈0.05）. The physical function and general health in WJ-MSCs group were all better than control group during the same period（P〈0.05）. Conclusion WJ-MSC transplantation via coronary can significantly improve the left ventricular function, reduce left ventricular volume, delay or prevent left ventricular remodeling for at least 18 months, and improve the quality of life and daily activity for 24 months in patients with ischemic heart failure with safety and efficacy.