Abstract
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.
Highlights
Stem cells have been reported to recover damaged hearts from myocardial infarction and have been investigated for use in myocardial regeneration [1,2,3]
To evaluate the cytotoxicity of histochrome in human Cardiac progenitor cells (CPCs), hCPCs were treated with different concentrations of histochrome for 24 h
No change in the morphology of hCPCs was observed on pretreatment with 0 μM, 5 μM, 10 μM, and 20 μM concentrations of histochrome (Figure 1C)
Summary
Stem cells have been reported to recover damaged hearts from myocardial infarction and have been investigated for use in myocardial regeneration [1,2,3]. CPCs are classified as a prevailing stem cell population in the heart and have crucial roles in cardiac homeostasis [5,6]. Recent preclinical studies suggest that transplantation of CPCs into the ischemic myocardium can significantly improve cardiac regeneration via the formation of vasculature and new myocytes [8,9,10]. CPCs have the potential to produce and remodel extracellular matrix (ECM) proteins [11], trigger CPC proliferation, and stimulate growth factor secretion [12]. According to these positive results, CPC might be a promising stem cell source in cardiovascular regeneration. Increasing the survival of CPCs can be a beneficial strategy to enhance the therapeutic effect in ischemic heart disease
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