PMID- 26162993 OWN - NLM STAT- MEDLINE DCOM- 20160112 LR - 20220317 IS - 1741-7015 (Electronic) IS - 1741-7015 (Linking) VI - 13 DP - 2015 Jul 10 TI - Intracoronary infusion of Wharton's jelly-derived mesenchymal stem cells in acute myocardial infarction: double-blind, randomized controlled trial. PG - 162 LID - 10.1186/s12916-015-0399-z [doi] LID - 162 AB - 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). FAU - Gao, Lian R AU - Gao LR AD - Center of Cardiology, Navy General Hospital, Beijing, China. lianrugao668@yahoo.com. FAU - Chen, Yu AU - Chen Y AD - Center of Cardiology, Navy General Hospital, Beijing, China. yuchen911@hotmail.com. FAU - Zhang, Ning K AU - Zhang NK AD - Center of Cardiology, Navy General Hospital, Beijing, China. zhangningkun2004@163.com. FAU - Yang, Xi L AU - Yang XL AD - Department of Cardiology, the First People's Hospital of Foshan, Guangdong Province, Foshan, China. yxli@fsyyy.com. FAU - Liu, Hui L AU - Liu HL AD - Department of Cardiology, General Hospital of Armed Police Forces, Beijing, China. lhl518@vip.sina.com. FAU - Wang, Zhi G AU - Wang ZG AD - Center of Cardiology, Navy General Hospital, Beijing, China. wzgzyhwsj@163.com. FAU - Yan, Xiao Y AU - Yan XY AD - Department of Biostatistics, Peking University First Hospital, the Clinical Research Institute of Peking University, Beijing, China. xiaoyan.y@foxmail.com. FAU - Wang, Yu AU - Wang Y AD - Department of Age Cardiology, the General Hospital of Chinese PLA, Beijing, China. wangyuheart@yeah.net. FAU - Zhu, Zhi M AU - Zhu ZM AD - Center of Cardiology, Navy General Hospital, Beijing, China. zhuzhiming6542@sina.com. FAU - Li, Tian C AU - Li TC AD - Center of Cardiology, Navy General Hospital, Beijing, China. ltc909@aliyun.com. FAU - Wang, Li H AU - Wang LH AD - Center of Cardiology, Navy General Hospital, Beijing, China. wanglihua66666@163.com. FAU - Chen, Hai Y AU - Chen HY AD - Center of Cardiology, Navy General Hospital, Beijing, China. jjhchy@163.com. FAU - Chen, Yun D AU - Chen YD AD - Department of Cardiology, the General Hospital of Chinese People's Liberation Army, Beijing, China. cyundai@medmail.com.cn. FAU - Huang, Chao L AU - Huang CL AD - Department of Cardiology, Beijing Huaxin Hospital, Beijing, China. huangchaolian@hotmail.com. FAU - Qu, Peng AU - Qu P AD - Department of Cardiology, the Second Affiliated Hospital of Dalian Medical University, Liaoning Province, Dalian, China. qupeng777@aliyun.com. FAU - Yao, Chen AU - Yao C AD - Department of Biostatistics, Peking University First Hospital, the Clinical Research Institute of Peking University, Beijing, China. yaochen@hsc.pku.edu.cn. FAU - Wang, Bin AU - Wang B AD - Department of Cardiology, the Central Hospital of Aerospace Corporation, Beijing, China. asch369@126.com. FAU - Chen, Guang H AU - Chen GH AD - Department of Cardiology, the General Hospital of Chinese People's Liberation Army, Beijing, China. chenkevin301@msn.com. FAU - Wang, Zhong M AU - Wang ZM AD - Department of Cardiology, General Hospital of Huabei Oilfield, Huabei Province, Renqiu, China. zhongmingw@163.com. FAU - Xu, Zhao Y AU - Xu ZY AD - Department of Cardiology, the First People's Hospital of Foshan, Guangdong Province, Foshan, China. yannihu@126.com. FAU - Bai, Jing AU - Bai J AD - Department of Age Cardiology, the General Hospital of Chinese PLA, Beijing, China. doctor_r16@163.com. FAU - Lu, Di AU - Lu D AD - Department of Cardiology, Central Hospital of National Petroleum Corporation, Huabei Province, Langfang, China. doctorludi@163.com. FAU - Shen, Yan H AU - Shen YH AD - Department of Ultrasonic Diagnosis, Navy General Hospital, Beijing, China. bjyanhua@aliyun.com. FAU - Guo, Feng AU - Guo F AD - Department of Nuclear Medicine, Navy General Hospital, Beijing, China. guofeng_gf84@126.com. FAU - Liu, Mu Y AU - Liu MY AD - Shenzhen Beike Cell Engineering Research Institute, Guangdong Province, Shenzhen, China. muyun@beike.cc. FAU - Yang, Yong AU - Yang Y AD - Department of Cardiology, General Hospital of Armed Police Forces, Beijing, China. yangyongfmmu@163.com. FAU - Ding, Yan C AU - Ding YC AD - Department of Cardiology, the Second Affiliated Hospital of Dalian Medical University, Liaoning Province, Dalian, China. yanchunding@aliyun.com. FAU - Yang, Ye AU - Yang Y AD - Center of Cardiology, Navy General Hospital, Beijing, China. yangye0407@sina.com. FAU - Tian, Hai T AU - Tian HT AD - Center of Cardiology, Navy General Hospital, Beijing, China. tianhaitao1973@sina.com. FAU - Ding, Qing A AU - Ding QA AD - Center of Cardiology, Navy General Hospital, Beijing, China. dingqingai2013@163.com. FAU - Li, Li N AU - Li LN AD - Department of Cardiology, Beijing Huaxin Hospital, Beijing, China. linali2006@gmail.com. FAU - Yang, Xin C AU - Yang XC AD - Department of Cardiology, Beijing Chaoyang Hospital of Capital Medical University, Beijing, China. yangxc99@gmail.coma. FAU - Hu, Xiang AU - Hu X AD - Shenzhen Beike Cell Engineering Research Institute, Guangdong Province, Shenzhen, China. huxiang@beike.cc. LA - eng SI - ClinicalTrials.gov/NCT01291329 GR - K01 AA020102/AA/NIAAA NIH HHS/United States GR - R03 AA020101/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20150710 PL - England TA - BMC Med JT - BMC medicine JID - 101190723 SB - IM MH - Adult MH - Aged MH - Double-Blind Method MH - Echocardiography MH - Female MH - Humans MH - Male MH - Mesenchymal Stem Cell Transplantation/*methods MH - Middle Aged MH - Myocardial Infarction/*therapy MH - Tomography, Emission-Computed, Single-Photon MH - Treatment Outcome MH - Ventricular Function, Left MH - Wharton Jelly PMC - PMC4499169 EDAT- 2015/07/15 06:00 MHDA- 2016/01/13 06:00 PMCR- 2015/07/10 CRDT- 2015/07/12 06:00 PHST- 2015/03/04 00:00 [received] PHST- 2015/06/12 00:00 [accepted] PHST- 2015/07/12 06:00 [entrez] PHST- 2015/07/15 06:00 [pubmed] PHST- 2016/01/13 06:00 [medline] PHST- 2015/07/10 00:00 [pmc-release] AID - 10.1186/s12916-015-0399-z [pii] AID - 399 [pii] AID - 10.1186/s12916-015-0399-z [doi] PST - epublish SO - BMC Med. 2015 Jul 10;13:162. doi: 10.1186/s12916-015-0399-z.