1. Epicardial injection of Ad-HGF activates endogenous
c-kit+ cardiac stem cells and fosters survival and regeneration of the infarcted aged heart
Jiabao Liu, PhD
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

2. Background
[1] Stem Cells Jul;32(7): [2] Nature 2011; 473: 326–335. [3] J Am Coll Cardiol Aug 23;58(9):
[4] Lancet 2012; 379: 895–904.

3. Background
Hepatocyte growth factor (HGF) is a multifunctional cytokine that exerts considerable biological effects including cell growth, anti-fibrogenic, wound repair, tissue homeostasis etc..
[1] Eur J Vasc Endovasc Surg. 2014 Oct;48(4):430-7.
[2] Cell Mol Life Sci May;68(10):

4. Our previous studies
Our precious studies have demonstrated adenovirus carrying the HGF gene (Ad-HGF) plays an indispensable role in the neovascularization and heart function preservation after MI.
However whether Ad-HGF could promote the proliferation and differentiation of endogenous c-kit positive CSCs is still largely unknown.
[1] PLoS One. 2013;8(1):e [2] Curr Gene Ther Feb;14(1):63-73.

5. Objective of this study
This study aims to determine whether injection of Ad-HGF into the infarction border zone of aged rat following MI can promote the proliferation and differentiation of endogenous c-kit positive CSCs and thus improve cardiac remodeling.

6. A positive correlation between the expression levels of HGF and c-kit+ CSCs in rat heart of different age stages

7. Ad-HGF treatment increased the protein expression
of HGF and p-Met in aged infarcted heart
N, normal zone;
P, peri-infarct zone;
I, infarct zone.

8. Ad-HGF increased the number of c-kit+ CSCs in aged infarcted heart

9. Ad-HGF promotes proliferation and differentiation
of c-kit+ CSCs in aged infarcted heart

10. Ad-HGF promotes the cardiomyocyte regeneration
and angiogenesis in aged infarcted heart

11. Ad-HGF activates the Akt-p21/p27-cell cycle pathway

12. Ad-HGF reduces apoptosis in 28th day’s heart

13. Ad-HGF improves the cardiac remodeling
of 28th day’s heart following MI

14. Summary
Notably, we discovered the expression levels of HGF/p-Met and c-kit+ CSCs gradually decreased with age increasing and showed a positive correlation between them.
Ad-HGF treatment activated endogenous c-kit+ CSCs and promoted cardiomyocyte proliferation and angiogenesis, thus improved the cardiac remodeling of the aged rat following MI.

15. THANK YOU