Journal
BASIC RESEARCH IN CARDIOLOGY
Volume 114, Issue 2, Pages -Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00395-019-0718-1
Keywords
Cellular post-conditioning; Sympathetic nervous system; Fibrosis; Stem cells; Ischemia-reperfusion injury; Cell therapy; Left ventricular function
Categories
Funding
- National Heart, Lung, and Blood Institute, Bethesda, MD (National Institutes of Health) [1R01 HL092141, 1R01 HL093579, 1U24 HL 094373, 1P20 HL113452, R01 HL133835, 18CDA34110445]
- American Heart Association, Dallas, TX, Career Development Award
- LSU Medical School Foundation
- LSU Medical School Alumni Association, New Orleans, LA
Ask authors/readers for more resources
Enthusiasm for cell therapy for myocardial injury has waned due to equivocal benefits in clinical trials. In an attempt to improve efficacy, we investigated repeated cell therapy and adjunct renal denervation (RDN) as strategies for augmenting cardioprotection with cardiosphere-derived cells (CDCs). We hypothesized that combining CDC post-conditioning with repeated CDC doses or delayed RDN therapy would result in superior function and remodeling. Wistar-Kyoto (WKY) rats or spontaneously hypertensive rats (SHR) were subjected to 45min of coronary artery ligation followed by reperfusion for 12-14weeks. In the first study arm, SHR were treated with CDCs (0.5 x 10(6) i.c.) or PBS 20min following reperfusion, or additionally treated with CDCs (1.0 x 10(6) i.v.) at 2, 4, and 8weeks. In the second arm, at 4weeks following myocardial infarction (MI), SHR received CDCs (0.5 x 10(6) i.c.) or CDCs+RDN. In the third arm, WKY rats were treated with i.c. CDCs administered 20min following reperfusion and RDN or a sham at 4weeks. Early i.c.+multiple i.v. dosing, but not single i.c. dosing, of CDCs improved long-term left ventricular (LV) function, but not remodeling. Delayed CDC+RDN therapy was not superior to single-dose delayed CDC therapy. Early CDC+delayed RDN therapy improved LV ejection fraction and remodeling compared to both CDCs alone and RDN alone. Given that both RDN and CDCs are currently in the clinic, our findings motivate further translation targeting a heart failure indication with combined approaches.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available