10.25376/hra.7811699.v1
David Polhemus
David
Polhemus
Rishi Trivedi
Rishi
Trivedi
Thomas Sharp
Thomas
Sharp
Zhen Li
Zhen
Li
Traci Goodchild
Traci
Goodchild
Amy Scarborough
Amy
Scarborough
Geoffrey de Couto
Geoffrey
de Couto
Eduardo Marbán
Eduardo
Marbán
David J. Lefer
David J.
Lefer
Polhemus.BRC.Repeated cell transplan denervation.2019.pdf
Health Research Alliance
2019
Cardioprotection
Cardiosphere-derived cells
Renal Denervation
Cardiology (incl. Cardiovascular Diseases)
2019-03-06 21:30:29
Journal contribution
https://hra.figshare.com/articles/journal_contribution/Polhemus_BRC_Repeated_cell_transplan_denervation_2019_pdf/7811699
<p>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 45 min of coronary artery ligation followed by reperfusion
for 12–14 weeks. In the first study arm, SHR were treated with CDCs (0.5 × 106 i.c.)
or PBS 20 min following reperfusion, or additionally treated with CDCs (1.0 ×
106 i.v.) at 2, 4, and 8 weeks. In the second arm, at 4 weeks following
myocardial infarction (MI), SHR received CDCs (0.5 × 106 i.c.) or CDCs + RDN.
In the third arm, WKY rats were treated with i.c. CDCs administered 20 min
following reperfusion and RDN or a sham at 4 weeks. 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.</p>