Julie Laloy

University of Namur, Belgium

Title: In vitro and in vivo models of cardiac ischemia : Past and Future

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Biography

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Abstract

Myocardial ischemia-reperfusion injury is a frequent event in the clinic. To avoid myocardial irreversible injury (like infarction), causes of ischemia need to be removed within 20 minutes after onset. Many drugs for cardiac disease treatment have demonstrated promising results in preclinical studies but the benefits cannot be demonstrated in large clinical trials. It appears thus important to identify the failure to translate developed promising drugs from preclinical studies to practice. It can be attributed to the reliance on cell and small animal models of preclinical studies, and to the pathogenesis mechanism of ischemia-reperfusion injury not fully understood.

For animal model, they cannot fully recapitulate human cardiac physiology due to limitation of using nonreperfused myocardial infarction and reperfused myocardial infarction. For in vitro models, isolated cardiomyocytes allow studies of the direct effect of therapeutics on cardiomyocytes with easy management of external factors in simulated ischemia-reperfusion impacting mechanisms that drive ischemia-reperfusion injury. But these models present limitations due to the lack of adult cardiac stem cells availability and the low turnover of mature cardiomyocytes. Some promising new models are under development like cardiomyocytes derived from human induced pluripotent stem cells that are more resistant to hypoxia than the mature cells, tissue engineering platforms to promote cardiomyocyte maturation, or 3D cell culture for a more predictive physiologic response.

Thereby, the development of more relevant in vitro and in vivo models of cardiac ischemia-reperfusion are thus necessary to facilitate translation from research into clinical practice.