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Intramyocardial Cell Delivery: Observations in Murine Hearts
Published on: January 24, 2014
Human embryonic stem cell-derived cardiomyocytes engraft but do not alter cardiac remodeling after chronic infarction
S Fernandes1, A V Naumova, W Z Zhu
1Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA.
Insights
Human embryonic stem cell-derived cardiomyocytes (hESC-CM) can survive and engraft in chronic heart attack models. However, hESC-CM transplantation did not improve cardiac function or remodeling in this chronic myocardial infarction model.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Stem Cell Biology
Background:
- Previous studies demonstrated human embryonic stem cell-derived cardiomyocytes (hESC-CM) preserve function in acute myocardial infarction models.
- Established heart failure patients may benefit from cell transplantation, necessitating research in chronic models.
Purpose of the Study:
- To evaluate the physiological effects of hESC-CM transplanted into a chronic myocardial infarction model.
- To assess cardiac structure and function following hESC-CM injection in rats with established heart failure.
Main Methods:
- Intramyocardial injection of hESC-CM with a pro-survival cocktail (PSC) into rats 1 month post-ischemia-reperfusion.
- Comparison with control groups: serum-free media, PSC only, and non-cardiac human cells in PSC.
- Evaluation of left ventricular function via echocardiography and MRI at 1, 2, and 3 months post-injection.
Main Results:
- Histology confirmed survival, sarcomere organization, and proliferation of human cardiomyocytes at 3 months.
- No significant differences in left ventricular structure or function were observed between groups.
- hESC-CM transplantation did not alter cardiac remodeling in the chronic infarct model.
Conclusions:
- hESC-CM can engraft and survive in chronic infarct models, similar to acute models.
- The current hESC-CM injection protocol is insufficient to restore function or alter remodeling in chronic myocardial infarction.
- Further research is needed to optimize cell therapy for chronic heart failure.
Abstract:
Previous studies indicated that, in an acute myocardial infarction model, human embryonic stem cell-derived cardiomyocytes (hESC-CM) injected with a pro-survival cocktail (PSC) can preserve contractile function. Because patients with established heart failure may also benefit from cell transplantation, we evaluated the physiological effects of hESC-CM transplanted into a chronic model of myocardial infarction. Intramyocardial injection of hESC-CM with PSC was performed in nude rats at 1 month following ischemia-reperfusion. The left ventricular function of hESC-CM injected rats was evaluated at 1, 2 and 3 months after the cell injection procedure and was compared to 3 control groups (rats injected with serum-free media, PSC only, or non-cardiac human cells in PSC). Histology at 3 months revealed that human cardiomyocytes survive, develop increased sarcomere organization and are still proliferating. Despite successful engraftment, both echocardiography and MRI analyses showed no significant difference in left ventricular structure or function between these 4 groups at any time point of the study, suggesting that human cardiomyocytes do not affect cardiac remodeling in a rat model of chronic myocardial infarction. When injected into a chronic infarct model, hESC-CM can engraft, survive and form grafts with striated cardiomyocytes at least as well as was previously observed in an acute myocardial infarction model. However, although hESC-CM transplantation can attenuate the progression of heart failure in an acute model, the same hESC-CM injection protocol is insufficient to restore heart function or to alter adverse remodeling of a chronic myocardial infarction model.
