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

Abstract

BackgroundThe 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).MethodsIn 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.ResultsDuring 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).ConclusionsIntracoronary 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 registrationClinical Trials NCT01291329 (02/05/2011).

Adult Stem Cell Therapy and Heart Failure, 2000 to 2016

“…More recently, Gao et al reported that intracoronary infusion of MSCs derived from umbilical cord obtained from healthy donors after full term birth resulted in a significant improvement in LVEF, LV volumes, and perfusion compared to controls at 18 months. 25 It should be emphasized, however, that given the limited number of studies performed using MSCs and the relatively small sample size in each study, definitive conclusions regarding the efficacy of this cell population cannot be made at the present. Additional studies with larger sample sizes using MSCs are needed to validate these findings.…”

“…24 Although it remains unclear how biologically similar MSCs from various tissue sources are, both BM- and non-BM-derived (e.g., adipose tissue) MSCs, as well as “pre-conditioned” cardiopoietic MSCs, have been increasingly tested in cell therapy studies. 25,26 Isolation, expansion, and purification of MSCs, however, can be a long and tedious process, which may limit the large-scale production of these cells for clinical transplantation.…”

Human Umbilical Cord-Derived Mesenchymal Stromal Cells Improve Left Ventricular Function, Perfusion, and Remodeling in a Porcine Model of Chronic Myocardial Ischemia

“…Zhang et al reported that UC‐MSCs can improve ventricular remodeling and function in a porcine model of AMI [24]. Recently, a clinical trial evaluated the effect of UC‐MSCs in AMI and found that LVEF increased and LVESV and LVEDV decreased significantly [14]. However, until now, there has been no report about the use of UC‐MSCs in the treatment of chronic heart ischemia.…”

“…Until now, many clinical studies used UC‐MSCs to treat graft‐versus‐host disease [11], cirrhosis [12], or diabetes mellitus [13]. A recent clinical study used UC‐MSCs to treat acute myocardial infarction (AMI) and demonstrated that intracoronary delivery of UC‐MSCs was safe and could significantly improve myocardial viability and heart function [14]. However, there are as yet no data about the effect of UC‐MSCs on chronic myocardial ischemia.…”

Looking Beyond Reperfusion

“…To address these issues, a number of approaches to the modification of MSCs with the aim to improve their survival and proliferation, to reduce the immune reaction, enhance transdifferentiation, and optimize the profile of secreted paracrine factors have been tested [69]. 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 [70,71]. The discovery of adult cardiac stem cells (CSCs) and their potential to restore functional cardiac tissue has fuelled unprecedented interest in recent years.…”