23.4.2 - Different ways to treat osteoarthritis with mesenchymal stromal cells injection: an animal model
- E. Antonioli (São Paulo, BR)
- E. Antonioli (São Paulo, BR)
- F. Bruno Dias De Oliveira (Sao Paulo, BR)
- O. Metropolo Dias (Sao Paulo, BR)
- J. Gabriel Souza (Sao Paulo, BR)
- M. Ferretti (São Paulo, BR)
Abstract
Purpose
Osteoarthritis(OA) treatment using mesenchymal stromal cells(MSC) has been extensively used and still there is no consensus regarding the number of cells applications and the best transplantation route. Using destabilization of the medial meniscus(DMM) as a model of OA, the aims of this study was to track MSC after intra-articular(IA) and intravenous(IV) injections, analyzing cytokines kinetics and histological structure.
Methods and Materials
OA was induced in female Wistar Kyoto rats via the DMM surgery. Rat bone marrow MSC was transduced with Luciferase transgene. Animals were treated with MSC after 9 weeks of surgery, via IA-MSC (2x106cells/kg) and IV-MSC (4x106cells/kg) injection. In vivo assay was acquired using the imaging system IN-VIVO MSFX PRO and the luminescence kinetic curve. Serum cytokines concentrations were determined with multiplex assay. Images and cytokines were analyzed at time intervals between 2h to 1 week after the transplant. After 4 and 12 weeks post-MSC treatment, knee was assessed by cartilage histology by OARSI score. Statistical analyzes were performed by Student's t-Test, one/two-way ANOVA.
Results
Viable MSC was observed in the OA knee until 1 week after the IA-MSC injection, and only until 8h in IV-MSC injection. The cytokines showed a different fluctuation concentration depended on the method of administration and time. IV-MSC injection increases MIP-1alpha and IL10 after 2h, decreasing in 24h, while MCP1 decreases after 2h. The opposite was observed with IA-MSC injection which increases MCP1 at the same time point, in addition to increase IL18 after 24h. Both cytokines decreased after 1 week. The OARSI score was better in both cell treatments than placebo. However, the IA-MSC showed a trend to reduce cartilage degeneration over time.
Conclusion
There is a possible homing capacity of MSC to the OA injury joint when injected IV. Taken together the results suggest that there is a longer lasting effect of MSC when injected via IA.