Combination Therapy of Mesenchymal Stromal Cells and Interleukin-4 Attenuates Rheumatoid Arthritis in a Collagen-Induced Murine Model
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Collagen-Induced Arthritis Model
2.3. Preparation of BM-Derived MSCs
2.4. Experimental Design
2.5. Biochemical Analysis of Rheumatoid Markers
2.6. RNA Isolation and Reverse Transcription
2.7. Quantitative Real-Time PCR
2.8. Analysis of Knee Joint Histopathology
2.9. Statistical Analysis
3. Results
3.1. Combined MSCs and IL-4 Treatment Showed Best Improvement in Biochemical Markers of RA
3.2. Combined MSCs and IL-4 Attenuated RA via Anti-Inflammatory Action
3.3. Combined MSCs and IL-4 Attenuated Articular Cartilage Degradation and Positively Affected Connective Tissue Remodeling of Synovial Tissue
3.4. Combined MSCs and IL-4 Improve the Histopathological Changes in the Knee Joint
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Gene | Primer Sequence | |
---|---|---|
Forward Primer | Reverse Primer | |
Comp1 | 5′- ATGGTCTTACGGGGAGATGCC -3′ | 5′- GAGAGGTTTCTGGAGCCTTTTGG -3′ |
Mmp1 | 5′- TTGTTGCTGCCCATGAGCTT -3′ | 5′- ACTTTGTCGCCAATTCCAGG -3′ |
Timp1 | 5′- GCATCTGGCATCCTCTTGTT-3′ | 5′- TGGGGAACCCATGAATTTAG-3′ |
Il1r | 5′- TGAGGTCTTGGAGGGACAGT -3′ | 5′- TGGCCCAACATGACTAAGGG -3′ |
β-actin | 5′- ACTGCCGCATCCTCTTCCTC – 3′ | 5′- ACTCCTGCTTGCTGATCCACAT -3′ |
Histopathological Alterations | Groups | ||||
---|---|---|---|---|---|
Healthy Control | CIA | MSCs | IL-4 | MSCs+ IL-4 | |
Hyperplasia of synovial lining layer | 0 | 3 | 0 | 0 | 0 |
Infiltration of leukocytes into synovial membrane | 0 | 3 | 1 | 1 | 0 |
Pannus formation | 0 | 2 | 0 | 1 | 0 |
Necrosis/erosion of cartilage | 0 | 3 | 0 | 1 | 0 |
Final Arthritis Score | 0 | 11 | 1 | 3 | 0 |
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Haikal, S.M.; Abdeltawab, N.F.; Rashed, L.A.; Abd El-Galil, T.I.; Elmalt, H.A.; Amin, M.A. Combination Therapy of Mesenchymal Stromal Cells and Interleukin-4 Attenuates Rheumatoid Arthritis in a Collagen-Induced Murine Model. Cells 2019, 8, 823. https://doi.org/10.3390/cells8080823
Haikal SM, Abdeltawab NF, Rashed LA, Abd El-Galil TI, Elmalt HA, Amin MA. Combination Therapy of Mesenchymal Stromal Cells and Interleukin-4 Attenuates Rheumatoid Arthritis in a Collagen-Induced Murine Model. Cells. 2019; 8(8):823. https://doi.org/10.3390/cells8080823
Chicago/Turabian StyleHaikal, Shaimaa M., Nourtan F. Abdeltawab, Laila A. Rashed, Tarek I. Abd El-Galil, Heba A. Elmalt, and Magdy A. Amin. 2019. "Combination Therapy of Mesenchymal Stromal Cells and Interleukin-4 Attenuates Rheumatoid Arthritis in a Collagen-Induced Murine Model" Cells 8, no. 8: 823. https://doi.org/10.3390/cells8080823