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Published on: May 25, 2020
Cardiac resynchronization by cardiosphere-derived stem cell transplantation in an experimental model of myocardial
Michael Bonios1, Connie Y Chang, Aurelio Pinheiro
1Johns Hopkins University, 720 Rutland Avenue, Baltimore, MD 21210, USA.
Insights
Cardiosphere-derived stem cell (CDC) transplantation improved heart function after myocardial infarction (MI). CDCs enhanced ejection fraction by improving regional strain and reducing dyssynchrony in the infarct zone.
Area of Science:
- Regenerative Medicine
- Cardiology
- Stem Cell Therapy
Background:
- Myocardial infarction (MI) often leads to impaired global and regional cardiac function.
- Cardiosphere-derived stem cells (CDCs) show potential for improving left ventricular ejection fraction (LVEF) post-MI.
- The impact of CDCs on regional function and cardiac dyssynchrony remains to be fully elucidated.
Purpose of the Study:
- To investigate the effects of CDC transplantation on regional cardiac function and dyssynchrony following myocardial infarction.
- To assess the therapeutic potential of CDCs in restoring mechanical synchrony in the infarcted heart.
Main Methods:
- Rat CDCs or saline were injected into the infarct regions of Wistar Kyoto rats (n=7 per group).
- Infarct size and CDC localization were assessed using positron emission tomography.
- Two-dimensional and strain echocardiography were employed to measure LVEF, circumferential strain, and dyssynchrony at 1 and 4 weeks post-MI.
Main Results:
- CDC transplantation significantly improved LVEF, circumferential strain, and reduced dyssynchrony in the infarct/peri-infarct zone by 4 weeks post-MI.
- In contrast, the saline group showed deterioration in LVEF and circumferential strain, with no change in dyssynchrony.
- Improved LVEF correlated with enhanced circumferential strain and reduced dyssynchrony in the CDC group.
Conclusions:
- CDC therapy effectively enhances LVEF by improving regional myocardial mechanics and decreasing dyssynchrony in the post-MI setting.
- Cellular resynchronization with CDCs presents a promising alternative to traditional electrical resynchronization for managing post-MI dyssynchrony.
Background:
Cardiosphere-derived stem cell (CDC) transplantation can improve global left ventricular ejection fraction (LVEF) after myocardial infarction (MI). The aim of this study was to examine the effects of CDC transplantation on regional function and dyssynchrony after MI.
Methods:
Two million rat CDCs (n = 7) or phosphate-buffered saline (n = 7) was injected into the infarct regions of Wistar Kyoto rats. Infarct size and CDC localization were evaluated by positron emission tomography (n = 7). Two-dimensional and strain echocardiography were performed at 1 and 4 weeks after MI. LVEF, circumferential strain, and time to peak circumferential strain were measured in the basal and apical short-axis views. Dyssynchrony was defined as the maximal difference of time to peak circumferential strain of opposing segments in each short-axis view. Engraftment was measured by quantitative polymerase chain reaction.
Results:
Positron emission tomography revealed that infarct size was 15.4 ± 3.6% of the left ventricle and that CDCs were localized to the infarct and border zone. CDC transplantation improved mean LVEF (45 ± 8% to 52 ± 7%, P = .02), mean circumferential strain (-7 ± 2% to -10 ± 1%, P = .02), and mean dyssynchrony (45 ± 10 to 28 ± 11 m sec, P = .04) of the infarct/peri-infarct zone from 1 to 4 weeks after MI, despite CDC engraftment of only 2.4 ± 3%. In contrast, mean LVEF (48 ± 5% to 40 ± 4%, P = .03) and mean circumferential strain (-8 ± 2% to -7 ± 1%, P = .02) of the infarcted region deteriorated, with no significant change in dyssynchrony (42 ± 12 vs 46 ± 13 m sec, P = .60) in the saline group during the same time period. Change in LVEF was correlated with change in circumferential strain (r = -0.8, P = .002) and dyssynchrony (r = 0.6, P = .02) of the infarct/peri-infarct region at 4 weeks after MI.
Conclusions:
CDC therapy enhanced LVEF by improving circumferential strain and decreasing dyssynchrony of the infarct/peri-infarct region at 4 weeks, but not 1 week, after MI. Cellular resynchronization therapy using CDCs may be an alternative to traditional electrical cellular resynchronization therapy in post-MI dyssynchrony.
