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

Lian R Gao, Yu Chen, Ning K Zhang, Xi L Yang, Hui L Liu, Zhi G Wang, Xiao Y Yan, Yu Wang, Zhi M Zhu, Tian C Li, Li H Wang, Hai Y Chen, Yun D Chen, Chao L Huang, Peng Qu, Chen Yao, Bin Wang, Guang H Chen, Zhong M Wang, Zhao Y Xu, Jing Bai, Di Lu, Yan H Shen, Feng Guo, Mu Y Liu, Yong Yang, Yan C Ding, Ye Yang, Hai T Tian, Qing A Ding, Li N Li, Xin C Yang, Xiang Hu, Lian R Gao, Yu Chen, Ning K Zhang, Xi L Yang, Hui L Liu, Zhi G Wang, Xiao Y Yan, Yu Wang, Zhi M Zhu, Tian C Li, Li H Wang, Hai Y Chen, Yun D Chen, Chao L Huang, Peng Qu, Chen Yao, Bin Wang, Guang H Chen, Zhong M Wang, Zhao Y Xu, Jing Bai, Di Lu, Yan H Shen, Feng Guo, Mu Y Liu, Yong Yang, Yan C Ding, Ye Yang, Hai T Tian, Qing A Ding, Li N Li, Xin C Yang, Xiang Hu

Abstract

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).

Figures

Fig. 1
Fig. 1
Enrollment and outcomes
Fig. 2
Fig. 2
a Mean F-18-FDG-PET signal intensity in the infarct vessel area measured before and four months after transplantation. Comparison of mean F-18-FDG-PET signal intensity changes and absolute changes between the WJMSC group and the placebo group using analysis of covariance (ANCOVA). T-bars show the standard errors. b Mean signal intensity of 99mTc-MIBI perfusion imaging in the infarcted vessel area measured before and four months after transplantation. Comparison of mean 99mTc-MIBI signal intensity changes and absolute changes between the WJMSC group and the placebo group by ANCOVA. T-bars show the standard errors WJMSC Wharton’s jelly-derived mesenchymal stem cells
Fig. 3
Fig. 3
a Comparison of changes in the global left ventricular ejection fraction (LVEF) between the WJMSC group and the placebo group measured by two dimensional-echocardiograph before transplantation and at the 4-, 12- and 18-month follow-ups. b. The absolute changes in LVEF, LVESV and LVEDV between the WJMSC group and the placebo group at 18 months measured by ECG and analyzed by ANCOVA. T-bars show the standard errors ANCOVA analysis of covariance, ECG echocardiogram, LVEDV left ventricular end-diastolic volume, LVESV left ventricular end-systolic volume, WJMSC Wharton’s jelly-derived mesenchymal stem cells

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