RT Journal Article
SR Electronic
T1 Effect of Human Mesenchymal Stem Cells on Freund’s adjuvant-induced Rheumatoid Arthritis in Sprague Dawley Rats
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.12.20.473415
DO 10.1101/2021.12.20.473415
A1 Satyen Sanghavi
A1 Vinayak Kedage
A1 Rajesh Pratap Singh
A1 Parvathi Chandran
A1 Vidya Jadhav
A1 Sujata Shinde
YR 2021
UL http://biorxiv.org/content/early/2021/12/21/2021.12.20.473415.abstract
AB Introduction Mesenchymal stem cells (MSC) therapy is a new approach to treat RA. Studies evaluating anti-inflammatory effects of MSCs per RA severity are scarce. Our primary objective was to evaluate anti-inflammatory effects, change in cytokine levels and cartilage regeneration of two different MSC preparations delivered through two different routes of administration in three RA stages: mild, moderate and severe.Methods Human-derived umbilical cord tissue MSCs (hUCT-MSCs) and human bone marrow-derived MSCs (hBM-MSCs) delivered via intra-plantar and intravenous routes were tested in Freund’s adjuvant-induced arthritis in rats. Arthritis severity was based on the arthritis score (<3=mild, 3=moderate and 4=severe). Assessments included changes in arthritis scoring, paw swelling, haematology parameters, biomarkers (TNFα and IL-10) and histopathology analysis.Results MSC treatment significantly reduced arthritis scores in all treatment groups. IL-10 levels increased 30 days after treatment with (IP)hUCT-MSCs (P=0.0241), (IV)hUCT-MSCs (P=0.0095) and (IP)hBM-MSCs (P=0.0002). TNF-α levels reduced compared to positive control at 30 days: (IP)hUCT-MSCs (P=0.0060), (IV)hUCT-MSCs (P=0.0003), (IP)hBM-MSCs (P=0.0005), (IV)hBM-MSCs (P<0.0001) and continued through 30-60 days. Microscopic examination showed regenerative changes in animal joints treated with both intra-plantar or intravenous MSCs. Arthritis scores reduced in all RA severity groups while benefits (changes in IL-10 and TNF-alpha) were more pronounced in moderate and severe RA. Haematology parameters remained similar among all animal groups at baseline, 30 days and 60 days indicating safety of MSCs.Conclusion Treatment with hUCT MSCs and hBM MSCs were safe, well-tolerated and effectively reduced joint inflammation, synovial cellularity and pro-inflammatory cytokine levels in CFA-induced RA rat model.Competing Interest StatementSatyen Sanghavi, Dr. Vinayak Kedage, Rajesh Pratap Singh, Parvathi Chandran, Vidhya Jadhav and Sujata Shinde are employees of Regrow Biosciences Pvt. Ltd.