Journal article
Cortical Bone Stem Cell Therapy Preserves Cardiac Structure and Function After Myocardial Infarction
Circulation research, v 121(11), pp 1263-1278
10 Nov 2017
PMCID: PMC5681384
PMID: 28912121
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Rationale: Cortical bone stem cells (CBSCs) have been shown to reduce ventricular remodeling and improve cardiac function in a murine myocardial infarction (MI) model. These effects were superior to other stem cell types that have been used in recent early-stage clinical trials. However, CBSC efficacy has not been tested in a preclinical large animal model using approaches that could be applied to patients.
Objective: To determine whether post-MI transendocardial injection of allogeneic CBSCs reduces pathological structural and functional remodeling and prevents the development of heart failure in a swine MI model.
Methods and Results: Female Gottingen swine underwent left anterior descending coronary artery occlusion, followed by reperfusion (ischemia-reperfusion MI). Animals received, in a randomized, blinded manner, 1:1 ratio, CBSCs (n=9; 2x10(7) cells total) or placebo (vehicle; n=9) through NOGA-guided transendocardial injections. 5-ethynyl-2'deoxyuridine (EdU)-a thymidine analog-containing minipumps were inserted at the time of MI induction. At 72 hours (n=8), initial injury and cell retention were assessed. At 3 months post-MI, cardiac structure and function were evaluated by serial echocardiography and terminal invasive hemodynamics. CBSCs were present in the MI border zone and proliferating at 72 hours post-MI but had no effect on initial cardiac injury or structure. At 3 months, CBSC-treated hearts had significantly reduced scar size, smaller myocytes, and increased myocyte nuclear density. Noninvasive echocardiographic measurements showed that left ventricular volumes and ejection fraction were significantly more preserved in CBSC-treated hearts, and invasive hemodynamic measurements documented improved cardiac structure and functional reserve. The number of EdU(+) cardiac myocytes was increased in CBSC-versus vehicle-treated animals.
Conclusions: CBSC administration into the MI border zone reduces pathological cardiac structural and functional remodeling and improves left ventricular functional reserve. These effects reduce those processes that can lead to heart failure with reduced ejection fraction.
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Details
- Title
- Cortical Bone Stem Cell Therapy Preserves Cardiac Structure and Function After Myocardial Infarction
- Creators
- Thomas E. Sharp - Temple UniversityGiana J. Schena - Temple UniversityAlexander R. Hobby - Temple UniversityTimothy Starosta - Temple UniversityRemus M. Berretta - Temple UniversityMarkus Wallner - Temple UniversityGiulia Borghetti - Temple UniversityPolina Gross - Temple UniversityDaohai Yu - Temple UniversityJaslyn Johnson - Temple UniversityEric Feldsott - Temple UniversityDanielle M. Trappanese - Temple UniversityAmir Toib - Temple UniversityJoseph E. Rabinowitz - Temple UniversityJon C. George - Temple UniversityHajime Kubo - Temple UniversitySadia Mohsin - Temple UniversitySteven R. Houser - Temple University
- Publication Details
- Circulation research, v 121(11), pp 1263-1278
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 16
- Grant note
- R56HL137850 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) P01HL108806-04; 1R56HL137850-01 / National Institute of Health, National Heart, Blood, and Lung Institute, Washington DC 14PRE20450006 / American Heart Association
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000414934100012
- Scopus ID
- 2-s2.0-85037712307
- Other Identifier
- 991021861852404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cardiac & Cardiovascular Systems
- Hematology
- Peripheral Vascular Disease