Myocardial infarction models in NOD/Scid mice for cell therapy research: permanent ischemia vs ischemia-reperfusion

Vanessa-Leigh van Zuylen1,2, Melina C den Haan1, Helene Roelofs2

  • 1Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, 2300 RC Leiden, The Netherlands.

Springerplus
|July 18, 2015
PubMed

Insights

This study compared permanent versus transient ischemia models for myocardial infarction (MI) in mice. Permanent ischemia better models MI for cell therapy research due to greater cardiac damage, despite transient ischemia better reflecting clinical reperfusion.

Area of Science:

  • Cardiovascular Research
  • Animal Models of Disease
  • Immunology

Background:

  • Myocardial infarction (MI) animal studies are crucial for understanding disease mechanisms and testing novel therapies.
  • Current models often use permanent coronary artery occlusion, which doesn't fully represent clinical scenarios where blood flow is frequently restored.
  • There is a need for experimental models that better mimic the transient nature of ischemia in human patients.

Purpose of the Study:

  • To compare permanent ischemia (PI) and transient ischemia-reperfusion (IR) models of myocardial infarction in immunodeficient NOD/Scid mice.
  • To evaluate the suitability of these models for investigating cell-based therapies for MI.
  • To assess the impact of different ischemia types on cardiac function, infarct size, and inflammatory responses.

Main Methods:

  • Induction of permanent ischemia (PI) and transient ischemia (45 minutes) followed by reperfusion (IR) in NOD/Scid mice.
  • Assessment of cardiac function, infarct size, cardiac wall thickness, and collagen deposition.
  • Quantification of cardiac inflammatory cells and serum cytokine levels.

Main Results:

  • PI mice exhibited significantly reduced cardiac function, infarct size, wall thickness, and collagen deposition compared to IR mice.
  • IR animals showed less dynamic changes in cardiac inflammatory cells and serum cytokine levels compared to PI animals.
  • MI induced significant changes in the inflammatory state, validating the use of this immunodeficient mouse strain for studying human cell therapy.

Conclusions:

  • While transient ischemia-reperfusion better reflects clinical practice, permanent ischemia induces more significant cardiac damage, making it more suitable for evaluating cell therapy efficacy.
  • The PI model provides a measurable therapeutic window for cell therapy investigations.
  • Immunodeficient NOD/Scid mice are valuable for studying human cell therapy in the context of myocardial infarction due to their inflammatory response to MI.

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