Abstract
BackgroundCardiac progenitor cells (CPCs) have been shown to be suitable in stem cell therapy for resurrecting damaged myocardium, but poor retention of transplanted cells in the ischemic myocardium causes ineffective cell therapy. Hypoxic preconditioning of cells can increase the expression of CXCR4 and pro-survival genes to promote better cell survival; however, it is unknown whether hypoxia preconditioning will influence the survival and retention of CPCs via the SDF-1α/CXCR4 axis.Methods and ResultsCPCs were isolated from adult mouse hearts and purified by magnetic activated cell sorting using c-kit magnetic beads. These cells were cultured at various times in either normoxic or hypoxic conditions, and cell survival was analyzed using flow cytometry and the expression of hypoxia-inducible factor-1α (HIF-1α), CXCR4, phosphorylated Akt and Bcl-2 were measured by Western blot. Results showed that the expression of pro-survival genes significantly increased after hypoxia treatment, especially in cells cultured in hypoxic conditions for six hours. Upon completion of hypoxia preconditioning from c-kit+ CPCs for six hours, the anti-apoptosis, migration and cardiac repair potential were evaluated. Results showed a significant enhancement in anti-apoptosis and migration in vitro, and better survival and cardiac function after being transplanted into acute myocardial infarction (MI) mice in vivo. The beneficial effects induced by hypoxia preconditioning of c-kit+ CPCs could largely be blocked by the addition of CXCR4 selective antagonist AMD3100.ConclusionsHypoxic preconditioning may improve the survival and retention of c-kit+ CPCs in the ischemic heart tissue through activating the SDF-1α/CXCR4 axis and the downstream anti-apoptosis pathway. Strategies targeting this aspect may enhance the effectiveness of cell-based cardiac regenerative therapy.
Highlights
Recent studies have accumulated compelling evidence suggesting that the adult heart has regeneration potential [1], but even the aging [2] and diseased heart [3] shows regenerative success
The results showed that vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1a (SDF-1a) significantly increased after hypoxic preconditioning compared with normoxia-cultured c-kit+ Cardiac progenitor cells (CPCs) (Figure 2F)
These results indicate that the therapeutic effects of c-kit+ CPC transplantation in a healing myocardial infarction (MI) were enhanced by hypoxia preconditioning via SDF-1/CXCR4 axis
Summary
Recent studies have accumulated compelling evidence suggesting that the adult heart has regeneration potential [1], but even the aging [2] and diseased heart [3] shows regenerative success. But more importantly in human beings, there are several populations of cardiac progenitor cells (CPCs) that reside in the heart [3,4,5,6,7] These resident CPCs are self-renewing, clonogenic, multipotent and have the ability to proliferate and spontaneously differentiate into either functional cardiomyocytes, smooth muscle cells or endothelial cells in vitro and in vivo [4,5,6,7]. Among these CPCs, c-kit positive cardiac progenitor cells have shown to be suitable in cell therapy for resurrecting injured myocardium [4,5]. Hypoxic preconditioning of cells can increase the expression of CXCR4 and pro-survival genes to promote better cell survival; it is unknown whether hypoxia preconditioning will influence the survival and retention of CPCs via the SDF-1a/ CXCR4 axis
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.