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Cytoprotective role of vitamin E in porcine adipose-tissue-derived mesenchymal stem cells against hydrogen-peroxide-induced oxidative stress

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Abstract

Survival of mesenchymal stem cells (MSCs) against oxidative stress and inflammation is vital for effective stem cell therapy. The reactive oxygen species (ROS) result in apoptosis and release of inflammatory mediators. Adipose-derived stem cells (ASCs) have shown promise for stem cell therapy owing to their anti-inflammatory and anti-oxidant activity. Previously, we showed the benefits of vitamin E against hydrogen peroxide (H2O2)-induced oxidative stress in rat bone marrow-derived MSCs. In this study, we aim to evaluate the effect of vitamin E treatment on porcine adipose-derived mesenchymal stem cells (pASCs) against H2O2-induced oxidative stress. The oxidative stress was induced by treating pASCs with 500 μM H2O2 with or without vitamin E. Viability of pASCs is enhanced after vitamin E treatment. In addition, reduced cellular toxicity, total NO level, PGE2 production and caspase-3 activity were observed after vitamin E treatment. Gene expression analysis of vitamin E-treated pASCs showed down-regulated expression for the genes associated with oxidative stress and apoptosis, viz., NOS2, Casp3, p53, BAX, MDM2, NFκB, HIF1α and VEGF-A genes. On the other hand, expression of anti-apoptotic and survival genes was up-regulated, viz., BCL2, BCL2L1 and MCL1. Furthermore, phosphorylation of Akt was attenuated following vitamin E treatment. The findings of this study may help in developing effective stem cell therapy for the diseases characterized by the oxidative stress and inflammation.

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Funding sources

This work was supported by grants from the Arthritis Foundation (Discovery award, H.C) and Oxnard Medical Research Foundation (H.C). K.A.H was supported by grants from the Department of Veterans Affairs (VA Merit Review Award) and (Research Career Scientist Award). A.K.Y. was supported by grants from NIH/NIAMS (AR064723).

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Authors and Affiliations

  1. Department of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center-Campbell Clinic, Memphis, TN, USA

    Fazal Ur Rehman Bhatti, Karen A. Hasty & Hongsik Cho

  2. Memphis VA Medical Center, Memphis, TN, USA

    Fazal Ur Rehman Bhatti, Karen A. Hasty & Hongsik Cho

  3. Kongju National University, Gongju, South Korea

    Song Ja Kim

  4. Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA

    Ae-Kyung Yi

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  1. Fazal Ur Rehman Bhatti
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  2. Song Ja Kim
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  3. Ae-Kyung Yi
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  4. Karen A. Hasty
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  5. Hongsik Cho
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Contributions

F. Bhatti, K. Hasty and H. Cho designed and performed the experiments. F. Bhatti, S.J. Kim and A.K. Yi performed the statistical analysis. F. Bhatti, K. Hasty and H. Cho wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Karen A. Hasty or Hongsik Cho.

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Supplementary Fig. 1

Optimization of H2O2 dose to treat pASCs. At 500 μM dose approximately 50% cytotoxicity was observed as compared to control group lyzed with 1% Triton X-100. The cytotoxicity at concentrations > 500 μM is obvious. Therefore a dose of 500 μM was selected for H2O2-induced stress. Data is represented as mean ± SD

High-resolution image (TIF 341 KB)

Supplementary Fig. 2

Optimization of Vitamin E dose to treat pASCs. The LDH release was least at 500 μM dose as compared to control group lyzed with 1% Triton X-100. The cytotoxicity at concentrations > 500 μM is obvious. Therefore a dose of 500 μM was selected for Vitamin E. The concentration of H2O2 was 500 μM. Data is represented as mean ± SD (GIF 318 KB)

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Bhatti, F.U.R., Kim, S.J., Yi, AK. et al. Cytoprotective role of vitamin E in porcine adipose-tissue-derived mesenchymal stem cells against hydrogen-peroxide-induced oxidative stress. Cell Tissue Res 374, 111–120 (2018). https://doi.org/10.1007/s00441-018-2857-3

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