title: Impaired redox environment modulates cardiogenic and ion-channel gene expression in cardiac-resident and non-resident mesenchymal stem cells.
abstract: Redox homeostasis plays a crucial role in the regulation of self-renewal and differentiation of stem cells. However, the behavioral actions of mesenchymal stem cells in redox imbalance state remain elusive. In the present study, the effect of redox imbalance that was induced by either hydrogen peroxide (H2O2) or ascorbic acid on human cardiac-resident (hC-MSCs) and non-resident (umbilical cord) mesenchymal stem cells (hUC-MSCs) was evaluated. Both cells were sensitive and responsive when exposed to either H2O2or ascorbic acid at a concentration of 400 µmol/L. Ascorbic acid pre-treated cells remarkably ameliorated the reactive oxygen species level when treated with H2O2. The endogenous antioxidative enzyme gene (Sod1, Sod2, TRXR1 and Gpx1) expressions were escalated in both MSCs in response to reactive oxygen species elevation. In contrast, ascorbic acid pre-treated hUC-MSCs attenuated considerable anti-oxidative gene (TRXR1 and Gpx1) expressions, but not the hC-MSCs. Similarly, the cardiogenic gene (Nkx 2.5, Gata4, Mlc2a and β-MHC) and ion-channel gene ( IKDR, IKCa, Itoand INa.TTX) expressions were significantly increased in both MSCs on the oxidative state. On the contrary, reduced environment could not alter the ion-channel gene expression and negatively regulated the cardiogenic gene expressions except for troponin-1 in both cells. In conclusion, redox imbalance potently alters the cardiac-resident and non-resident MSCs stemness, cardiogenic, and ion-channel gene expressions. In comparison with cardiac-resident MSC, non-resident umbilical cord-MSC has great potential to tolerate the redox imbalance and positively respond to cardiac regeneration. Impact statement Human mesenchymal stem cells (h-MSCs) are highly promising candidates for tissue repair in cardiovascular diseases. However, the retention of cells in the infarcted area has been a major challenge due to its poor viability and/or low survival rate after transplantation. The regenerative potential of mesenchymal stem cells (MSCs) repudiate and enter into premature senescence via oxidative stress. Thus, various strategies have been attempted to improve the MSC survival in 'toxic' conditions. Similarly, we investigated the response of cardiac resident MSC (hC-MSCs) and non-resident MSCs against the oxidative stress induced by H2O2. Supplementation of ascorbic acid (AA) into MSCs culture profoundly rescued the stem cells from oxidative stress induced by H2O2. Our data showed that the pre-treatment of AA is able to inhibit the cell death and thus preserving the viability and differentiation potential of MSCs.
authors.affiliation: 1 Nichi-Asia Life Science Sdn Bhd., Petaling Jaya 47810, Selangor, Malaysia.|2 Department of Microbiology, Bharathiyar University, Coimbatore, Tamil Nadu 641046, India.
authors.forename: Baskar
authors.initials: B
authors.lastname: Subramani
authors.affiliation: 1 Nichi-Asia Life Science Sdn Bhd., Petaling Jaya 47810, Selangor, Malaysia.
authors.forename: Sellamuthu
authors.initials: S
authors.lastname: Subbannagounder
authors.affiliation: 1 Nichi-Asia Life Science Sdn Bhd., Petaling Jaya 47810, Selangor, Malaysia.
authors.forename: Chithra
authors.initials: C
authors.lastname: Ramanathanpullai
authors.affiliation: 3 Department of Zoology, Arignar Anna Government Arts College, Namakkal, Tamil Nadu 637002, India.
authors.forename: Sekar
authors.initials: S
authors.lastname: Palanivel
authors.affiliation: 4 Stem Cell & Immunity Group, Immunology Laboratory, Department of Pathology, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang 43400, Malaysia.|5 Stem Cell Research Laboratory, Genetic and Regenerative Medicine Research Center, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Ramasamy
mesh_terms: D001205:Ascorbic Acid / Q000494:pharmacology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007473:Ion Channels; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid
keywords: Human umbilical cord mesenchymal stem cell; cardiac gene expression; human cardiac mesenchymal stem cell; ion-channel gene expression; oxidative stress; redox balance