Vitamin E protects rat mesenchymal stem cells against hydrogen peroxide-induced oxidative stress in vitro and improves their therapeutic potential in surgically-induced rat model of osteoarthritis.
Oxidative stress is a major obstacle against cartilage repair in osteoarthritis (OA). Anti-oxidant agents can play a vital role in addressing this issue. We evaluated the effect of Vitamin E preconditioning in improving the potential of mesenchymal stem cells (MSCs) to confer resistance against oxidative stress prevailing during OA.



Vitamin E pretreated MSCs were exposed to oxidative stress in vitro by hydrogen peroxide (H2O2) and also implanted in surgically-induced rat model of OA. Analysis was done in terms of cell proliferation, apoptosis, cytotoxicity, chondrogenesis and repair of cartilage tissue.



Vitamin E pretreatment enabled MSCs to counteract H2O2-induced oxidative stress in vitro. Proliferative markers, proliferating cell nuclear antigen (PCNA) and Ki67 were up-regulated, along with the increase in the viability of MSCs. Expression of transforming growth factor-beta (TGFβ) was also increased. Reduction of apoptosis, expression of vascular endothelial growth factor (VEGF) and caspase 3 (Casp3) genes, and lactate dehydrogenase (LDH) release were also observed. Transplantation of Vitamin E pretreated MSCs resulted in increased proteoglycan contents of cartilage matrix. Increased expression of chondrogenic markers, Aggrecan (Acan) and collagen type-II alpha (Col2a1) accompanied by decreased expression of collagen type-I alpha (Col1a1) resulted in increased differentiation index that signifies the formation of hyaline cartilage. Further, there was an increased expression of PCNA and TGFβ genes along with a decreased expression of Casp3 and VEGF genes with increased histological score.



Taken together results of this study demonstrated that Vitamin E pretreated MSCs have an improved ability to impede the progression of OA and thus increased potential to treat OA.
National Centre of Excellence in Molecular Biology, 87-West Canal Bank Road, University of the Punjab, Lahore, Pakistan; University of Tennessee Health Science Center-Campbell Clinic, Memphis, TN, USA. Electronic address: fbhatti@uthsc.edu.
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Bhatti
National Centre of Excellence in Molecular Biology, 87-West Canal Bank Road, University of the Punjab, Lahore, Pakistan. Electronic address: azra_mehmood@hotmail.com.
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Mehmood
National Centre of Excellence in Molecular Biology, 87-West Canal Bank Road, University of the Punjab, Lahore, Pakistan. Electronic address: noreenlatief@gmail.com.
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Latief
National Centre of Excellence in Molecular Biology, 87-West Canal Bank Road, University of the Punjab, Lahore, Pakistan. Electronic address: sanazaahra@gmail.com.
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Zahra
University of Tennessee Health Science Center-Campbell Clinic, Memphis, TN, USA; Veterans Affairs Medical Center, Memphis, TN, USA. Electronic address: hcho4@uthsc.edu.
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Cho
National Centre of Excellence in Molecular Biology, 87-West Canal Bank Road, University of the Punjab, Lahore, Pakistan. Electronic address: snkhan50@yahoo.com.
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Khan
National Centre of Excellence in Molecular Biology, 87-West Canal Bank Road, University of the Punjab, Lahore, Pakistan; Allama Iqbal Medical College, University of Health Sciences, Lahore, Pakistan. Electronic address: riazuddin@aimrc.org.
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Riazuddin
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000494:pharmacology* / Q000627:therapeutic use
D014810:Vitamin E; D006861:Hydrogen Peroxide
Antioxidant; Mesenchymal stem cells; Osteoarthritis; Oxidative stress; Vitamin E