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Anti-arthritic Effects of Undifferentiated and Chondrogenic Differentiated MSCs in MIA-induced Osteoarthritis in
Ablaa S Saleh1, Mohammed Abdel-Gabbar1, Hala Gabr2
1Biochemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.
Introduction:
Osteoarthritis (OA) is a degenerative joint disease that can affect the many tissues of the joint. There are no officially recognized disease-modifying therapies for clinical use at this time probably due to a lack of complete comprehension of the pathogenesis of the disease. In recent years, emerging regenerative therapy and treatments with stem cells both undifferentiated and differentiated cells have gained much attention as they can efficiently promote tissue repair and regeneration.
Methods:
To determine how bone marrow-derived mesenchymal stem cells (BM-MSCs) and chondrogenic differentiated MSCs (CD-MSCs) can treat OA in rats, OA was induced in Wistar rats by injecting three doses of 100 μL physiological saline containing 1 mg of MIA into rat ankle joint of the right hind leg for three consecutive days. Following the induction, the osteoarthritic rats were injected weekly with BM-MSCs or CD-MSCs at a dose of 1x106 cells/rat/dose for three weeks. In addition to morphological and histological investigations of the ankle, spectrophotometric, ELISA, and Western blot analyses were applied to detect various immunological and molecular parameters in serum and ankle.
Results:
The results of the study showed that in osteoarthritic rats, BM-MSCs and CD-MSCs significantly reduced right hind paw circumference, total leucocyte count (TLC), differential leukocyte count (DLC) of neutrophils, monocytes, lymphocytes, and eosinophils, serum rheumatoid factor (RF), prostaglandin E2 (PGE2) and interleukin (IL)-1β levels, while they elevated serum IL-10 level. Additionally, BM-MSCs and CD-MSCs markedly reduced lipid peroxides (LPO) levels while they elevated superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities. The monocyte chemoattractant protein-1 (MCP-1) level was significantly downregulated in ankle joint articular tissues by treatment with BM-MSCs or CD-MSCs while nuclear factor erythroid 2-related factor 2 (Nrf2) was upregulated; CD-MSCs treatment was more effective.
Conclusion:
According to these findings, it can be inferred that BM-MSCs and CD-MSCs have anti-arthritic potential in MIA-induced OA; CD-MSCs therapy is more effective than MSCs. The ameliorative anti-arthritic effects may be mediated by suppressing inflammation and oxidative stress through the downregulation of MCP-1 and upregulation of Nrf2. Based on the obtained results, BM-MSCs and CD-MSCs therapies are promising new options that can be associated with other clinical treatments to improve cartilage regeneration and joint healing. However, more preclinical and clinical research is required to assess the benefits and safety of treating osteoarthritic patients with BM-MSCs and CD-MSCs.
Insights
Bone marrow-derived mesenchymal stem cells (BM-MSCs) and chondrogenic differentiated MSCs (CD-MSCs) show potential in treating osteoarthritis (OA) in rats by reducing inflammation and oxidative stress. CD-MSCs demonstrated greater effectiveness than BM-MSCs in this preclinical study.
Area of Science:
- Regenerative Medicine
- Stem Cell Therapy
- Osteoarthritis Research
Background:
- Osteoarthritis (OA) is a degenerative joint disease with no current disease-modifying therapies.
- Stem cell therapies offer potential for tissue repair and regeneration in OA.
- Understanding OA pathogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To evaluate the therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) and chondrogenic differentiated MSCs (CD-MSCs) in a rat model of OA.
- To investigate the anti-inflammatory and antioxidant effects of these stem cell therapies.
Main Methods:
- Osteoarthritis was induced in Wistar rats using intra-articular injections of MIA.
- Rats received weekly injections of BM-MSCs or CD-MSCs for three weeks.
- Morphological, histological, and molecular analyses (ELISA, Western blot) were performed on serum and ankle tissues.
Main Results:
- Both BM-MSCs and CD-MSCs reduced paw swelling, inflammatory markers (TLC, DLC, RF, PGE2, IL-1β), and oxidative stress markers (LPO).
- Stem cell treatments increased anti-inflammatory IL-10 levels and antioxidant enzyme activities (SOD, GST).
- CD-MSCs were more effective than BM-MSCs in downregulating MCP-1 and upregulating Nrf2 in ankle tissues.
Conclusions:
- BM-MSCs and CD-MSCs exhibit anti-arthritic properties in a rat OA model, potentially by suppressing inflammation and oxidative stress.
- CD-MSC therapy appears more effective than BM-MSC therapy.
- These stem cell therapies are promising for cartilage regeneration and joint healing, warranting further preclinical and clinical research.
