BACKGROUND: Progenitor cells isolated from cardiac explant-derived cells improve cardiac function after myocardial infarction (MI). To fully realize the therapeutic potential of these cells, it is essential to develop a safe and efficient delivery method. Therefore, the objective of this study was to determine the efficacy of our newly developed approach to retrograde coronary vein (RCV) infusion of cardiac c-Kit(+) cells in a small-animal model of congestive heart failure (CHF). METHODS: Sprague-Dawley rats underwent experimental MI. After 21 days, cardiac explant-derived c-Kit(+) cells were delivered to both sham and CHF animals using RCV delivery. Vehicle-treated (serum-free medium) sham and CHF animals were used as controls. Cardiac function and heart tissues were evaluated 21 days post-transplantation. RESULTS: RCV-delivered cells were retained in infarcted hearts for at least 21 days after transplantation. At 21 days post-RCV infusion, the majority of transplanted c-Kit(+)/GFP(+) cells were localized in the left ventricle. Compared with vehicle-treated CHF animals, RCV-treated rats showed a significant improvement in cardiac function. Furthermore, RCV-treated rats exhibited an increase in capillary density, a decrease in total heart collagen, and a reduction in both infarct size and cardiomyocyte hypertrophy when compared with vehicle-treated CHF rats. CONCLUSIONS: Our study showed that the RCV infusion approach is an efficient technique for targeted cell delivery to the infarcted myocardium. Cardiac c-Kit(+) cells, delivered using RCV infusion ameliorated progression of heart failure, improved cardiac function and retarded myocardial remodeling in heart failure rats.
BACKGROUND: Progenitor cells isolated from cardiac explant-derived cells improve cardiac function after myocardial infarction (MI). To fully realize the therapeutic potential of these cells, it is essential to develop a safe and efficient delivery method. Therefore, the objective of this study was to determine the efficacy of our newly developed approach to retrograde coronary vein (RCV) infusion of cardiac c-Kit(+) cells in a small-animal model of congestive heart failure (CHF). METHODS:Sprague-Dawley rats underwent experimental MI. After 21 days, cardiac explant-derived c-Kit(+) cells were delivered to both sham and CHF animals using RCV delivery. Vehicle-treated (serum-free medium) sham and CHF animals were used as controls. Cardiac function and heart tissues were evaluated 21 days post-transplantation. RESULTS:RCV-delivered cells were retained in infarcted hearts for at least 21 days after transplantation. At 21 days post-RCV infusion, the majority of transplanted c-Kit(+)/GFP(+) cells were localized in the left ventricle. Compared with vehicle-treated CHF animals, RCV-treated rats showed a significant improvement in cardiac function. Furthermore, RCV-treated rats exhibited an increase in capillary density, a decrease in total heart collagen, and a reduction in both infarct size and cardiomyocyte hypertrophy when compared with vehicle-treated CHFrats. CONCLUSIONS: Our study showed that the RCV infusion approach is an efficient technique for targeted cell delivery to the infarcted myocardium. Cardiac c-Kit(+) cells, delivered using RCV infusion ameliorated progression of heart failure, improved cardiac function and retarded myocardial remodeling in heart failurerats.
Authors: Joshua K Salabei; Pawel K Lorkiewicz; Parul Mehra; Andrew A Gibb; Petra Haberzettl; Kyung U Hong; Xiaoli Wei; Xiang Zhang; Qianhong Li; Marcin Wysoczynski; Roberto Bolli; Aruni Bhatnagar; Bradford G Hill Journal: J Biol Chem Date: 2016-05-05 Impact factor: 5.157
Authors: Joshua K Salabei; Pawel K Lorkiewicz; Candice R Holden; Qianhong Li; Kyung U Hong; Roberto Bolli; Aruni Bhatnagar; Bradford G Hill Journal: Stem Cells Date: 2015-05-26 Impact factor: 6.277
Authors: Wouter A Gathier; Dirk Jan van Ginkel; Mira van der Naald; Frebus J van Slochteren; Pieter A Doevendans; Steven A J Chamuleau Journal: J Cardiovasc Transl Res Date: 2018-02-01 Impact factor: 4.132
Authors: K Dergilev; Z Tsokolaeva; P Makarevich; I Beloglazova; E Zubkova; M Boldyreva; E Ratner; D Dyikanov; M Menshikov; A Ovchinnikov; F Ageev; Ye Parfyonova Journal: Biomed Res Int Date: 2018-06-25 Impact factor: 3.411