Iron depletion with deferoxamine protects bone marrow-derived mesenchymal stem cells against oxidative stress-induced apoptosis

• Published in: Cell stress & chaperones Vol. 25; no. 6; pp. 1059 - 1069
• Main Authors: Khoshlahni, Nasrin, Sagha, Mohsen, Mirzapour, Tooba, Zarif, Mahin Nikougoftar, Mohammadzadeh-Vardin, Mohammad
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Science + Business Media 01.11.2020; Springer Netherlands; Springer Nature B.V
• Subjects: AKT protein; Animals; Apoptosis; Apoptosis - drug effects; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bone marrow; Cancer Research; Caspase 3 - metabolism; Caspase-3; Cell Biology; Cell culture; Cell self-renewal; Cell Shape - drug effects; Cell Survival - drug effects; Cell therapy; Cells, Cultured; Cytoprotection - drug effects; Cytotoxicity; Deferoxamine; Deferoxamine - pharmacology; Depletion; Down-Regulation - drug effects; Flow cytometry; Hydrogen peroxide; Hydrogen Peroxide - toxicity; Immunology; Immunophenotyping; Iron; Iron Deficiencies; Male; Mesenchymal stem cells; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - pathology; Neurosciences; Organs; ORIGINAL PAPER; Oxidative stress; Oxidative Stress - drug effects; Rats, Sprague-Dawley; Regenerative medicine; Staining; Stem cell transplantation; Stem cells; Toxicity; Oxidative stress; Deferoxamine; Mesenchymal stem cells; Apoptosis
• ISSN: 1355-8145; 1466-1268; 1466-1268
• DOI: 10.1007/s12192-020-01142-9

Bone marrow mesenchymal stem cells (BM-MSCs) are multipotent cells with self-renewal properties, making them an ideal candidate for regenerative medicine. Recently, numerous studies show that about more than 99% of transplanted cells are destroyed because of the stressful microenvironment. Meanwhile, in the target organs, iron overload can produce oxidative stress introducing it as the most important stress factor. The present study was aimed at increasing BM-MSCs’ viability against oxidative stress microenvironment using iron depletion by deferoxamine (DFO). Mesenchymal stem cells are isolated and characterized from rat bone marrow. Then, the sensitivity of BM-MSCs against H₂O₂-induced oxidative stress was evaluated through half of the inhibitory concentration (IC₅₀) estimation by using MTT assay. The maximum non-inhibitory concentration of DFO on BM-MSCs was determined. The next step was the comparison between DFO pre-treated BM-MSCs and untreated cells against H₂O₂-induced apoptosis. BM-MSCs were identified with morphologic and flow cytometry analysis. IC₅₀ of H₂O₂ was determined as 0.55 mM at 4 h. Also, the maximum non-inhibitory concentration of DFO was ascertained as 5 µM at 48 h. Our results demonstrated that pretreatment with DFO significantly potentiates BM-MSCs against H₂O₂-induced oxidative stress which was confirmed by MTT assay, AO/EB double staining, DAPI staining, and activated caspase 3 quantification as well as western blot test. Expression of cleaved caspase 3 and pAKT/AKT ratio obviously demonstrated DFO can resist the cells against cytotoxicity. These findings may help to develop better stem cell culture medium for MSC-based cell therapy. Moreover, regulation of cell stress can be used in practical subjects.