Cardiac progenitor cells (CPCs) are resident stem cells present in a small portion of ischemic hearts and function in repairing the damaged heart tissue. Intense oxidative stress impairs cell metabolism thereby decreasing cell viability. Protecting CPCs from undergoing cellular apoptosis during oxidative stress is crucial in optimizing
CPC-based
therapy.
Histochrome (
sodium salt of
echinochrome A-a common sea urchin pigment) is an
antioxidant drug that has been clinically used as a pharmacologic agent for
ischemia/reperfusion injury in Russia. However, the mechanistic effect of
histochrome on CPCs has never been reported. We investigated the protective effect of
histochrome pretreatment on human CPCs (hCPCs) against
hydrogen peroxide (H2O2)-induced oxidative stress.
Annexin V/7-aminoactinomycin D (7-AAD) assay revealed that
histochrome-treated CPCs showed significant protective effects against H2O2-induced cell death. The
anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and Bcl-xL were significantly upregulated, whereas the
pro-apoptotic proteins BCL2-associated X (Bax), H2O2-induced cleaved
caspase-3, and the DNA damage marker, phosphorylated
histone (γH2A.X) foci, were significantly downregulated upon
histochrome treatment of hCPCs in vitro. Further, prolonged incubation with
histochrome alleviated the replicative cellular senescence of hCPCs. In conclusion, we report the protective effect of
histochrome against oxidative stress and present the use of a potent and bio-safe cell priming agent as a potential therapeutic strategy in patient-derived hCPCs to treat
heart disease.