Abstract 2895: Mesenchymal Stem Cells Secrete VEGF and Protect Cardiomyocytes from Ischemia Reperfusion Injury through the PI3K Pathway
Previous data suggest that implantation of mesenchymal stem cells (MSC) preserve heart function after myocardial infarction. We hypothesized that MSC would protect cultured neonatal rat cardiomyocytes (NRC) from death induced by ischemia reperfusion (I/R) through a paracrin mechanism involving activation of the PI3K pathway by growth factors. Cyclosporin A (CsA) was used as a positive control for protection against I/R injury. beating NRC (2.10.6) were subjected to 5 hours of ischemia followed by 16 hours of reperfusion. At the time of reperfusion NRC (n=8–14/group) received either no treatment (control group), or CsA (200 nM in fresh DMEM), or MSC (2.10.5 MSC suspended in fresh DMEM), or SN/MSC (MSC supernatant after 8 hours of serum deprived culture), or LY294002 (SN/MSC + 15 μM of LY294002 a specific inhibitors of PI3K), or Wortmannin (SN/MSC + 100 nM of wortmannin, a non specific inhibitor of PI3K). VEGF, IGF-1, and HGF concentration in the preparations were measured by ELISA. Cell death was assessed by LDH release in NRC supernatant at the end of reperfusion. VEGF concentration was 559±3 pg/mL in SN/MSC and below detection level in the other groups. HGF and IGF-1 concentrations were below detection level in all groups. CsA induced a significant 96% reduction of LDH activity. MSC induced a 71% reduction of LDH activity. SN/MSC induced an 88% reduction that was blocked by addition of PI3K inhinbitors. our data suggest that MSC can protect cardiomyocytes from I/R injury through a paracrine mechanism mediated by activation of the PI3K pathway. In our model VEGF was the only growth factor possibly involved in this activation.