Mesenchymal stem cell (MSC)
transplantation is a promising approach in the
therapy of ischemic heart or
CNS diseases; however, the poor viability of MSCs after
transplantation critically limits the efficacy of this new strategy.
Prolyl hydroxylase inhibition followed by HIF-1alpha up-regulation participates in the regulation of apoptosis and cell survival, which have been shown in
cancer cells and neurons. The role of
prolyl hydroxylase inhibition by
dimethyloxalylglycine (DMOG) in regulation of cell survival has not been investigated in MSCs. In the present investigation with MSCs, apoptosis and cell death induced by serum deprivation were assessed by
caspase-3 activation and
trypan blue staining, respectively. The mitochondrial apoptotic pathway and PI3K/Akt cell survival pathway were evaluated. DMOG significantly attenuated apoptosis and cell death of MSCs, stabilized HIF-1alpha and induced downstream
glucose transport 1 (Glut-1) synthesis. DMOG treatment reduced mitochondrial
cytochrome c release, nuclear translocation of
apoptosis inducing factor (AIF), and promoted Akt phosphorylation. A specific PI3K inhibitor,
wortmannin, blocked Akt phosphorylation and abrogated the beneficial effect of DMOG. These data suggest that the DMOG protection of MSCs may provide a novel approach to promote cell survival during cell stress.