Effect of Stem Cell Transplantation, Methotrexate combined with Bevacizumab (Anti Vascular Endothelial Growth Factor) on The lung as one of Extra-articular tissues in Adjuvant-Induced Arthritis in Rats: A Pilot Study

Abstract

Rheumatoid arthritis is a chronic systemic inflammatory disease. Neoangiogenesis plays an important role in RA progression. RA is not only a joint disease but also affect extra-articular organs.

The pulmonary complications are a significant contributor to excess mortality in patients with rheumatoid arthritis ranking as the second major cause of death in this patient population. The lung not only affected by the disease it can be also affected by drugs for RA, like MTX which can lead to lung fibrosis.

Human umbilical cord blood mesenchymal stem cells may be a new therapy for RA and not to cause extra-articular damage even may cause extra-articular improvement. Also Bevacizumab as anti vascular endothelial growth factor can be a treatment for RA and may cause extra-articular improvement.

This thesis was carried out to study the effect of Stem Cell Transplantation, Methotrexate combined with Bevacizumab (Anti vascular endothelial growth factor) on the lung as one of extra-articular tissues in adjuvant-induced arthritis in rats and to be evaluated histopathologically with measuring anti-ccp level to evaluate and ensure disease progression and improvement, as it is highly specific for RA.

This study was performed on 32 adult male rats. RA was induced using Freund’s complete adjuvant intravenous in the tail vein twice with a week interval. Clinical score of the rats was assessed on day 20 after induction and 34 after treatment. Anticcp level was measured on day 20 after induction and 34 after treatment. Two rats were sacrificed on day 20 after induction to assess lung affection of obviously arthritic rats. Treatment started on day 21 after induction when the rats are obviously arthritic with clinical score ≥ 2. Group (A) injected intraperitoneally with mesenchymal stem cells, group (B) received methotrexate subcutaneously and group (C) was injected with methotrexate and bevacizumab. Six weeks after treatment all rats were sacrificed and their lungs were assessed histopathologically.

The present study revealed  The mean clinical score before treatment was 9.57 and after treatment all treated groups mean scores decreased with best improvement in both MSCs and Bevacizumab combined with MTX groups more than MTX group.

 Anti-ccp level, all rats had detectable anti-CCP it was detected in 100% of rats and positive (>5) in 80% of rats before treatment. While after treatment It decreased in 80% of rats in stem cell and methotrexate combined with bevacizumab group. 40% of rats showed decrease of anti-ccp titre in methotrexate group.

 Histopathologically there was obvious improvement and decrease of infiltration by inflammatory cells.20% of rats in both MSCs and combined groups showed best improvement while no rats in MTX group showed such improvement but MSCs group showed the best results.

Conclusion There was improvement in all treated groups .The results of Bevacizumab combined with Methotrexate group are close to stem cells group while the least improvement was in MTX group.