scholarly journals Combinatory Effects of Bone Marrow-Derived Mesenchymal Stem Cells and Indomethacin on Adjuvant-Induced Arthritis in Wistar Rats: Roles of IL-1β, IL-4, Nrf-2, and Oxidative Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Eman A. Ahmed ◽  
Osama M. Ahmed ◽  
Hanaa I. Fahim ◽  
Emad A. Mahdi ◽  
Tarek M. Ali ◽  
...  

Rheumatoid arthritis (RA) is a disorder triggered by autoimmune reactions and related with chronic inflammation and severe disability. Bone Marrow-derived Mesenchymal Stem Cells (BM-MSCs) have shown a hopeful immunomodulatory effect towards repairing cartilage and restoring joint function. Additionally, indomethacin (IMC), a nonsteroidal compound, has been considered as a potent therapeutic agent that exhibits significant antipyretic properties and analgesic effects. The target of the current research is to assess the antiarthritic efficacy of BM-MSCs (106 cells/rat at 1, 6, 12 and 18 days) and IMC (2 mg/kg body weight/day for 3 weeks) either alone or concurrently administered against complete Freund’s adjuvant-induced arthritic rats. Changes in paw volume, body weight, gross lesions, and antioxidant defense system, as well as oxidative stress, were assessed. The Th1 cytokine (IL-1β) serum level and Th2 cytokine (IL-4) and Nrf-2 ankle joint expression were detected. In comparison to normal rats, it was found that the CFA-induced arthritic rats exhibited significant leukocytosis and increase in paw volume, LPO level, RF, and IL-1β serum levels. In parallel, arthritic rats that received BM-MSCs and/or IMC efficiently exhibited decrease in paw edema, leukocytosis, and enhancement in the antioxidant enzymatic levels of SOD, GPx, GST, and GSH in serum besides upregulation of Nrf-2 and anti-inflammatory IL-4 expression levels in the ankle articular joint. Likewise, these analyses were more evidenced by the histopathological sections and histological score. The data also revealed that the combined administration of BM-MSC and IMC was more potent in suppressing inflammation and enhancing the anti-inflammatory pathway than each agent alone. Thus, it can be concluded that the combined therapy with BM-MSC and IMC may be used as a promising therapeutic choice after assessing their efficacy and safety in human beings with RA, and the antiarthritic effects may be mediated via modulatory effects on Th1/Th2 cytokines, ozidative stress, and Nrf-2.

2021 ◽  
Vol 10 ◽  
pp. 2131
Author(s):  
Majdedin Ghalavand ◽  
Hadi Esmaili Gouvarchin Ghaleh ◽  
Bahman Jalali Kondori ◽  
Javad Razaviyan ◽  
Samira Mohammadi-Yeganeh

Background: Alternate activation of monocytes could induce anti-inflammatory impacts. This study aimed to investigate whether monocyte cells treated with bone marrow mesenchymal stem cells supernatant (MSC-Sp) could improve anti-inflammatory responses as a cell transfer therapy for colitis. Materials and Methods: The induction of experimental colitis was done by acetic acid in four groups of male BALB/c mice, including the control colitis, treated-monocytes, non-treated-monocytes, and mesalazine groups. Following MSCs culture, the supernatant was harvested, and then 50% conditioned media, or negative control media was added to the monocytes for 24 h. After ten days, peritoneal injection of treated or non-treated-monocytes (105 cells/100µL) was performed in animals' relevant groups of colitis. Ten days later, the oxidative stress profile and histopathological evaluation of colon tissue were assessed. Results: Treated monocytes showed a significant improvement in the oxidative stress profile, namely myeloperoxidase (0.126±0.008), nitric oxide (0.153±0.01), and malondialdehyde (0.148±0.014) compared to the control colitis group (P<0.05). Also, histopathological results revealed that the rate of damage in the treated-monocytes group was less than in normal mice. Conclusion: Our study indicated that the treated monocytes had anti-oxidative potential in colitis mice and were usable as a complementary therapy. [GMJ.2021;10:e2131]


2014 ◽  
Vol 19 (5) ◽  
pp. 685-693 ◽  
Author(s):  
Bahareh Bahmani ◽  
Mehryar Habibi Roudkenar ◽  
Raheleh Halabian ◽  
Ali Jahanian-Najafabadi ◽  
Fatemeh Amiri ◽  
...  

Inflammation ◽  
2019 ◽  
Vol 43 (1) ◽  
pp. 123-134 ◽  
Author(s):  
E. S. Gad ◽  
A. A. A. Salama ◽  
M. F. El-Shafie ◽  
H. M. M. Arafa ◽  
R. M. Abdelsalam ◽  
...  

2020 ◽  
Vol 9 (6) ◽  
pp. 1711 ◽  
Author(s):  
Adrien A. Eshraghi ◽  
Emre Ocak ◽  
Angela Zhu ◽  
Jeenu Mittal ◽  
Camron Davies ◽  
...  

Recent advancements in stem cell therapy have led to an increased interest within the auditory community in exploring the potential of mesenchymal stem cells (MSCs) in the treatment of inner ear disorders. However, the biocompatibility of MSCs with the inner ear, especially when delivered non-surgically and in the immunocompetent cochlea, is not completely understood. In this study, we determined the effect of intratympanic administration of rodent bone marrow MSCs (BM-MSCs) on the inner ear in an immunocompetent rat model. The administration of MSCs did not lead to the generation of any oxidative stress in the rat inner ear. There was no significant production of proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-12, due to BM-MSCs administration into the rat cochlea. BM-MSCs do not activate caspase 3 pathway, which plays a central role in sensory cell damage. Additionally, transferase dUTP nick end labeling (TUNEL) staining determined that there was no significant cell death associated with the administration of BM-MSCs. The results of the present study suggest that trans-tympanic administration of BM-MSCs does not result in oxidative stress or inflammatory response in the immunocompetent rat cochlea.


2013 ◽  
Vol 25 (05) ◽  
pp. 1340010 ◽  
Author(s):  
Wen-Tyng Li ◽  
Wen-Kai Hu ◽  
Feng-Ming Ho

Diabetes mellitus (DM) is associated with bone loss and leads to osteopenia and osteoporosis. This study was undertaken to investigate whether the impaired functions of mesenchymal stem cells (MSCs) derived from bone marrow play a role in pathogenesis of DM-associated bone loss. Bone marrow MSCs were taken from the alloxan-induced diabetic rats and normal rats. Bone mineral densities of tibias and femurs in diabetic rats decreased compared to those of normal rats as shown by dual energy X-ray absorptiometry. MSCs from diabetic rats exhibited reduced colony formation activity. The in vitro effects of high glucose (HG) (20 or 33 mM) on the growth, oxidative stress, apoptosis, and differentiation MSCs were next assessed. The viability and proliferation of MSCs derived from diabetic rats decreased significantly compared with that from normal rats. HG further suppressed the proliferation and viability of MSCs from both diabetic and normal rats. HG was associated with 38–40% increase in reactive oxygen species level and had significantly downregulated the activities of superoxide dismutase (SOD) and catalase (CAT) which could be recovered by the addition of L-ascorbic acid. The phenomena of apoptosis such as chromatin condensation and DNA fragmentation were found in cells cultured under HG conditions. As compared with 5.5 mM glucose, exposure of MSCs to HG enhanced adipogenic induction of triacylglycerol accumulation and inhibited osteogenic induction of alkaline phosphatase activity. HG increased peroxisome proliferator-activated receptor gamma expression during adipogenesis and reduced RUNX2 expression during osteoblastogenesis. These results indicate that MSCs derived from diabetic rats exhibited the inhibitory effects on cell growth and osteogenic ability. The oxidative stress, apoptosis, and adipogenic capability of MSCs were increased by HG. Furthermore, it is suggested that HG induces bone loss via attenuating the proliferation and osteoblastogenesis and enhancing adipogenesis mediated by the oxidative stress in rat bone marrow MSCs.


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