Intracoronary infusion of Wharton's jelly-derived mesenchymal stem cells in acute myocardial infarction: double-blind, randomized controlled trial.

Author(s): Gao LR(1), Chen Y(2), Zhang NK(3), Yang XL(4), Liu HL(5), Wang ZG(6), Yan XY(7), Wang Y(8), Zhu ZM(9), Li TC(10), Wang LH(11), Chen HY(12), Chen YD(13), Huang CL(14), Qu P(15), Yao C(16), Wang B(17), Chen GH(18), Wang ZM(19), Xu ZY(20), Bai J(21), Lu D(22), Shen YH(23), Guo F(24), Liu MY(25), Yang Y(26), Ding YC(27), Yang Y(28), Tian HT(29), Ding QA(30), Li LN(31), Yang XC(32), Hu X(33).

Affiliation(s): Author information: (1)Center of Cardiology, Navy General Hospital, Beijing, China. lianrugao668@yahoo.com. (2)Center of Cardiology, Navy General Hospital, Beijing, China. yuchen911@hotmail.com. (3)Center of Cardiology, Navy General Hospital, Beijing, China. zhangningkun2004@163.com. (4)Department of Cardiology, the First People's Hospital of Foshan, Guangdong Province, Foshan, China. yxli@fsyyy.com. (5)Department of Cardiology, General Hospital of Armed Police Forces, Beijing, China. lhl518@vip.sina.com. (6)Center of Cardiology, Navy General Hospital, Beijing, China. wzgzyhwsj@163.com. (7)Department of Biostatistics, Peking University First Hospital, the Clinical Research Institute of Peking University, Beijing, China. xiaoyan.y@foxmail.com. (8)Department of Age Cardiology, the General Hospital of Chinese PLA, Beijing, China. wangyuheart@yeah.net. (9)Center of Cardiology, Navy General Hospital, Beijing, China. zhuzhiming6542@sina.com. (10)Center of Cardiology, Navy General Hospital, Beijing, China. ltc909@aliyun.com. (11)Center of Cardiology, Navy General Hospital, Beijing, China. wanglihua66666@163.com. (12)Center of Cardiology, Navy General Hospital, Beijing, China. jjhchy@163.com. (13)Department of Cardiology, the General Hospital of Chinese People's Liberation Army, Beijing, China. cyundai@medmail.com.cn. (14)Department of Cardiology, Beijing Huaxin Hospital, Beijing, China. huangchaolian@hotmail.com. (15)Department of Cardiology, the Second Affiliated Hospital of Dalian Medical University, Liaoning Province, Dalian, China. qupeng777@aliyun.com. (16)Department of Biostatistics, Peking University First Hospital, the Clinical Research Institute of Peking University, Beijing, China. yaochen@hsc.pku.edu.cn. (17)Department of Cardiology, the Central Hospital of Aerospace Corporation, Beijing, China. asch369@126.com. (18)Department of Cardiology, the General Hospital of Chinese People's Liberation Army, Beijing, China. chenkevin301@msn.com. (19)Department of Cardiology, General Hospital of Huabei Oilfield, Huabei Province, Renqiu, China. zhongmingw@163.com. (20)Department of Cardiology, the First People's Hospital of Foshan, Guangdong Province, Foshan, China. yannihu@126.com. (21)Department of Age Cardiology, the General Hospital of Chinese PLA, Beijing, China. doctor_r16@163.com. (22)Department of Cardiology, Central Hospital of National Petroleum Corporation, Huabei Province, Langfang, China. doctorludi@163.com. (23)Department of Ultrasonic Diagnosis, Navy General Hospital, Beijing, China. bjyanhua@aliyun.com. (24)Department of Nuclear Medicine, Navy General Hospital, Beijing, China. guofeng_gf84@126.com. (25)Shenzhen Beike Cell Engineering Research Institute, Guangdong Province, Shenzhen, China. muyun@beike.cc. (26)Department of Cardiology, General Hospital of Armed Police Forces, Beijing, China. yangyongfmmu@163.com. (27)Department of Cardiology, the Second Affiliated Hospital of Dalian Medical University, Liaoning Province, Dalian, China. yanchunding@aliyun.com. (28)Center of Cardiology, Navy General Hospital, Beijing, China. yangye0407@sina.com. (29)Center of Cardiology, Navy General Hospital, Beijing, China. tianhaitao1973@sina.com. (30)Center of Cardiology, Navy General Hospital, Beijing, China. dingqingai2013@163.com. (31)Department of Cardiology, Beijing Huaxin Hospital, Beijing, China. linali2006@gmail.com. (32)Department of Cardiology, Beijing Chaoyang Hospital of Capital Medical University, Beijing, China. yangxc99@gmail.coma. (33)Shenzhen Beike Cell Engineering Research Institute, Guangdong Province, Shenzhen, China. huxiang@beike.cc.

Publication date & source: 2015, BMC Med. , 13:162

BACKGROUND: The use of adult stem cells is limited by the quality and quantity of host stem cells. It has been demonstrated that Wharton's jelly-derived mesenchymal stem cells (WJMSCs), a primitive stromal population, could integrate into ischemic cardiac tissues and significantly improve heart function. In this randomized, controlled trial, our aim was to assess the safety and efficacy of intracoronary WJMSCs in patients with ST-elevation acute myocardial infarction (AMI). METHODS: In a multicenter trial, 116 patients with acute ST-elevation MI were randomly assigned to receive an intracoronary infusion of WJMSCs or placebo into the infarct artery at five to seven days after successful reperfusion therapy. The primary endpoint of safety: the incidence of adverse events (AEs) within 18 months, was monitored and quantified. The endpoint of efficacy: the absolute changes in myocardial viability and perfusion of the infarcted region from baseline to four months, global left ventricular ejection fraction (LVEF) from baseline to 18 months were measured using F-18-fluorodeoxyglucose positron emission computed tomography (F-18-FDG-PET) and 99mTc-sestamibi single-photon emission computed tomography (99mTc-SPECT), and two-dimensional echocardiography, respectively. RESULTS: During 18 months follow-up, AEs rates and laboratory tests including tumor, immune, and hematologic indexes were not different between the two groups. The absolute increase in the myocardial viability (PET) and perfusion within the infarcted territory (SPECT) was significantly greater in the WJMSC group [6.9 ± 0.6 % (95 %CI, 5.7 to 8.2)] and [7.1 ± 0.8 % (95 %CI, 5.4 to 8.8) than in the placebo group [3.3 ± 0.7 % (95 %CI, 1.8 to 4.7), P <0.0001] and 3.9 ± 0.6(95 %CI, 2.8 to 5.0), P = 0.002] at four months. The absolute increase in the LVEF at 18 months in the WJMSC group was significantly greater than that in the placebo group [7.8 ± 0.9 (6.0 to approximately 9.7) vs. 2.8 ± 1.2 (0.4 to approximately 5.1), P = 0.001]. Concomitantly, the absolute decreases in LV end-systolic volumes and end-diastolic volumes at 18 months in the WJMSC group were significantly greater than those in the placebo group (P = 0.0004, P = 0.004, respectively). CONCLUSIONS: Intracoronary infusion of WJMSCs is safe and effective in patients with AMI, providing clinically relevant therapy within a favorable time window. This study encourages additional clinical trials to determine whether WJMSCs may serve as a novel alternative to BMSCs for cardiac stem cell-based therapy. TRIAL REGISTRATION: Clinical Trials NCT01291329 (02/05/2011).