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Updated: May 4, 2026
Intramyocardial Cell Delivery: Observations in Murine Hearts
Published on: January 24, 2014
Effect of the use and timing of bone marrow mononuclear cell delivery on left ventricular function after acute
Jay H Traverse1, Timothy D Henry, Carl J Pepine
1Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis, Minnesota, USA.
Insights
Intracoronary bone marrow mononuclear cells (BMCs) did not improve left ventricular function after ST-segment elevation myocardial infarction (STEMI). The timing of BMC delivery, whether at 3 or 7 days post-reperfusion, also showed no significant effect on cardiac recovery compared to placebo.
Area of Science:
- Cardiovascular Medicine
- Regenerative Medicine
- Clinical Trials
Background:
- Cell therapy delivery after ST-segment elevation myocardial infarction (STEMI) has been explored, but the impact of timing on left ventricular function remains unclear.
- Previous trials have evaluated cell therapy for STEMI, necessitating further analysis of treatment timing's influence on cardiac recovery.
Purpose of the Study:
- To assess the effect of intracoronary autologous bone marrow mononuclear cell (BMC) delivery on global and regional left ventricular function recovery post-STEMI.
- To determine if the timing of BMC delivery (3 days vs. 7 days after reperfusion) impacts the recovery of left ventricular function.
Main Methods:
- A randomized, double-blind, placebo-controlled trial (Timing In Myocardial infarction Evaluation - TIME) involving 120 patients with STEMI and left ventricular dysfunction.
- Patients received intracoronary BMCs (150 × 10^6) or placebo, administered either 3 or 7 days after primary percutaneous coronary intervention (PCI).
- Cardiac magnetic resonance imaging was used to evaluate changes in global (LVEF) and regional left ventricular function at 6 months.
Main Results:
- No significant improvement in global left ventricular ejection fraction (LVEF) was observed in the BMC group compared to placebo at 6 months (48.3% vs. 47.8%).
- Treatment timing (day 3 vs. day 7) did not significantly affect the change in global or regional left ventricular function.
- Major adverse cardiovascular events were infrequent across all treatment arms.
Conclusions:
- Intracoronary administration of autologous bone marrow mononuclear cells (BMCs) 3 or 7 days after STEMI and primary PCI did not significantly improve left ventricular function recovery compared to placebo.
- The timing of BMC delivery did not influence the recovery of global or regional left ventricular function in patients following STEMI.
Context:
While the delivery of cell therapy after ST-segment elevation myocardial infarction (STEMI) has been evaluated in previous clinical trials, the influence of the timing of cell delivery on the effect on left ventricular function has not been analyzed.
Objectives:
To determine the effect of intracoronary autologous bone marrow mononuclear cell (BMC) delivery after STEMI on recovery of global and regional left ventricular function and whether timing of BMC delivery (3 days vs 7 days after reperfusion) influences this effect.
Design, Setting, And Patients:
A randomized, 2 × 2 factorial, double-blind, placebo-controlled trial, Timing In Myocardial infarction Evaluation (TIME) enrolled 120 patients with left ventricular dysfunction (left ventricular ejection fraction [LVEF] ≤ 45%) after successful primary percutaneous coronary intervention (PCI) of anterior STEMI between July 17, 2008, and November 15, 2011, as part of the Cardiovascular Cell Therapy Research Network sponsored by the National Heart, Lung, and Blood Institute.
Interventions:
Intracoronary infusion of 150 × 106 BMCs or placebo (randomized 2:1) within 12 hours of aspiration and cell processing administered at day 3 or day 7 (randomized 1:1) after treatment with PCI.
Main Outcome Measures:
The primary end points were change in global (LVEF) and regional (wall motion) left ventricular function in infarct and border zones at 6 months measured by cardiac magnetic resonance imaging and change in left ventricular function as affected by timing of treatment on day 3 vs day 7. The secondary end points included major adverse cardiovascular events as well as changes in left ventricular volumes and infarct size.
Results:
The mean (SD) patient age was 56.9 (10.9) years and 87.5% of participants were male. At 6 months, there was no significant increase in LVEF for the BMC group (45.2% [95% CI, 42.8% to 47.6%] to 48.3% [95% CI, 45.3% to 51.3%) vs the placebo group (44.5% [95% CI, 41.0% to 48.0%] to 47.8% [95% CI, 43.4% to 52.2%]) (P = .96). There was no significant treatment effect on regional left ventricular function observed in either infarct or border zones. There were no significant differences in change in global left ventricular function for patients treated at day 3 (−0.9% [95% CI, −6.6% to 4.9%], P = .76) or day 7 (1.1% [95% CI, −4.7% to 6.9%], P = .70). The timing of treatment had no significant effect on regional left ventricular function recovery. Major adverse events were rare among all treatment groups.
Conclusion:
Among patients with STEMI treated with primary PCI, the administration of intracoronary BMCs at either 3 days or 7 days after the event had no significant effect on recovery of global or regional left ventricular function compared with placebo.
Trial Registration:
clinicaltrials.gov Identifier: NCT00684021.
