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Delayed Intramyocardial Delivery of Stem Cells after Ischemia Reperfusion Injury in a Murine Model
Published on: September 3, 2020
Cortical Bone Stem Cell Therapy Preserves Cardiac Structure and Function After Myocardial Infarction
Thomas E Sharp1, Giana J Schena1, Alexander R Hobby1
1From the Department of Physiology, Cardiovascular Research Center (T.E.S., G.J.S., A.R.H., T.S., R.M.B., M.W., G.B., P.G., J.J., E.F., D.M.T., A.T., J.C.G., H.K., S.M., S.R.H.), Department of Clinical Sciences, Temple Clinical Research Institute (D.Y.), and Department of Pharmacology, Center for Translational Medicine (J.E.R.), Temple University Lewis Katz School of Medicine, Philadelphia, PA; Department of Cardiology, Temple University Hospital, Philadelphia, PA (J.C.G.); Section of Pediatric Cardiology, St. Christopher's Hospital for Children, Philadelphia, PA (A.T.); and Department of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (T.S.).
Cortical bone stem cells (CBSCs) improved heart function after myocardial infarction (MI) in a large animal model. CBSC treatment reduced scar size and preserved ejection fraction, offering potential for heart failure treatment.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Stem Cell Biology
Background:
- Cortical bone stem cells (CBSCs) demonstrated efficacy in reducing ventricular remodeling and improving cardiac function in murine myocardial infarction (MI) models.
- CBSC effects surpassed other stem cell types used in early clinical trials.
- Previous studies lacked preclinical validation in large animal models for patient-relevant approaches.
Purpose of the Study:
- To evaluate the efficacy of transendocardial injection of allogeneic CBSCs in reducing pathological remodeling and preventing heart failure post-MI in a swine model.
- To assess the impact of CBSCs on cardiac structure and function following induced myocardial infarction.
Main Methods:
- Swine underwent ischemia-reperfusion MI via left anterior descending coronary artery occlusion.
- Animals received randomized, blinded transendocardial injections of CBSCs (n=9) or placebo (vehicle; n=9).
- Cardiac structure and function were assessed using serial echocardiography and invasive hemodynamics at 3 months post-MI, with initial injury and cell retention evaluated at 72 hours.
Main Results:
- CBSCs were detected and proliferating in the MI border zone at 72 hours but did not affect initial injury.
- At 3 months, CBSC treatment significantly reduced scar size, decreased myocyte size, and increased myocyte nuclear density.
- Left ventricular volumes and ejection fraction were better preserved in CBSC-treated hearts, with improved cardiac functional reserve.
Conclusions:
- CBSC administration into the MI border zone effectively mitigates pathological cardiac remodeling.
- Treatment improves left ventricular functional reserve and reduces processes leading to heart failure with reduced ejection fraction.
- CBSCs represent a promising therapeutic strategy for post-myocardial infarction recovery.
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