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Assessment of the Immunomodulatory Properties of Human Mesenchymal Stem Cells MSCs
Published on: December 24, 2015
Pretreatment with Lycopene Attenuates Oxidative Stress-Induced Apoptosis in Human Mesenchymal Stem Cells
Ji Yong Kim1, Jai-Sung Lee2, Yong-Seok Han3
1Laboratory for Vascular Medicine & Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
Abstract:
Human mesenchymal stem cells (MSCs) have been used in cell-based therapy to promote revascularization after peripheral or myocardial ischemia. High levels of reactive oxygen species (ROS) are involved in the senescence and apoptosis of MSCs, causing defective neovascularization. Here, we examined the effect of the natural antioxidant lycopene on oxidative stress-induced apoptosis in MSCs. Although H2O2 (200 μM) increased intracellular ROS levels in human MSCs, lycopene (10 μM) pretreatment suppressed H2O2-induced ROS generation and increased survival. H2O2-induced ROS increased the levels of phosphorylated p38 mitogen activated protein kinase (MAPK), Jun-N-terminal kinase (JNK), ataxia telangiectasia mutated (ATM), and p53, which were inhibited by lycopene pretreatment. Furthermore, lycopene pretreatment decreased the expression of cleaved poly (ADP ribose) polymerase-1 (PARP-1) and caspase-3 and increased the expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax), which were induced by H2O2 treatment. Moreover, lycopene significantly increased manganese superoxide dismutase (MnSOD) expression and decreased cellular ROS levels via the PI3K-Akt pathway. Our findings show that lycopene pretreatment prevents ischemic injury by suppressing apoptosis-associated signal pathway and enhancing anti-oxidant protein, suggesting that lycopene could be developed as a beneficial broad-spectrum agent for the successful MSC transplantation in ischemic diseases.
Insights
Lycopene, a natural antioxidant, protects human mesenchymal stem cells (MSCs) from oxidative stress and apoptosis. This suggests lycopene can improve MSC transplantation for ischemic diseases by enhancing antioxidant defenses and survival.
Area of Science:
- Cell Biology
- Biochemistry
- Regenerative Medicine
Background:
- Mesenchymal stem cells (MSCs) are crucial for revascularization in ischemic conditions.
- Oxidative stress and reactive oxygen species (ROS) induce MSC apoptosis, impairing therapeutic efficacy.
- Developing strategies to protect MSCs from oxidative damage is vital for cell-based therapies.
Purpose of the Study:
- To investigate the protective effects of lycopene against oxidative stress-induced apoptosis in human MSCs.
- To elucidate the molecular mechanisms underlying lycopene's protective action.
- To assess lycopene's potential as an adjunct therapy for MSC transplantation in ischemic diseases.
Main Methods:
- Human MSCs were pretreated with lycopene before exposure to hydrogen peroxide (H2O2) to induce oxidative stress.
- Intracellular ROS levels, cell survival, and apoptosis markers (caspase-3, PARP-1, Bcl-2, Bax) were measured.
- Key signaling pathways involved in apoptosis and antioxidant defense (MAPK, ATM, p53, PI3K-Akt, MnSOD) were analyzed.
Main Results:
- Lycopene pretreatment significantly reduced H2O2-induced ROS generation and increased MSC survival.
- Lycopene inhibited the activation of pro-apoptotic signaling molecules (p38 MAPK, JNK, ATM, p53) and decreased cleaved PARP-1 and caspase-3 expression.
- Lycopene upregulated anti-apoptotic proteins (Bcl-2), downregulated pro-apoptotic proteins (Bax), and enhanced manganese superoxide dismutase (MnSOD) expression via the PI3K-Akt pathway.
Conclusions:
- Lycopene effectively protects human MSCs from oxidative stress and apoptosis by modulating key signaling pathways.
- Lycopene enhances the antioxidant capacity of MSCs, promoting their survival and therapeutic potential.
- Lycopene shows promise as a therapeutic agent to improve the efficacy of MSC transplantation in treating ischemic diseases.
