P012 - Up-Scale Manufactured Human Mesenchymal Stromal Cells Promote Murine Cartilage Regeneration
Abstract
Purpose
Autologous cell therapy is currently recommended by NICE for chondral/osteochondral injuries (https://www.nice.org.uk/guidance/ta477). Using allogeneic cells could significantly reduce production costs and transform cell therapy to a simple one-stage procedure. Human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs), which have shown promise in vitro, have been examined in a murine joint surface injury model, and compared to bone marrow (BM)-derived MSCs.
Methods and Materials
Full-thickness cartilage injuries were generated in the patellar groove of female, eight-to-ten week old Gdf5-Cre;Tom;Nes-GFP transgenic mice (n=54). At the time of injury, mice were injected intra-articularly with 2x105 hUC-MSCs (n=18) or hBM-MSCs (n=18) in 1µL of culture medium. All cells were grown in a Quantum® bioreactor and pooled from 3 individual donors. A third group received a vehicle control (1µL PBS; n=18). Joints were harvested eight-weeks post-injury. Cartilage repair (Fig 1) was assessed using the Wakitani grading system and immunohistochemically stained sections for collagen type II and ‘tomato’-positive cells (indicating embryological derivation from the joint interzone) were semi-quantitatively scored in the repair tissue.
Results
No mice showed any macroscopic signs of swelling/inflammation due to cell implantation. Both hMSC treatment groups had significantly lower mean Wakitani scores (i.e. better repair) compared with the vehicle control. Immunohistochemistry demonstrated that hUC-MSCs (but not hBM-MSCs) also had significantly more ‘tomato’-positive cells than the vehicle control, (indicating embryological derivation from the joint interzone) whereas collagen type II immunostaining showed no significant difference between the groups. Furthermore, a lower Wakitani score significantly correlated with increased collagen type II immunostaining and ‘tomato’-positive cells.
Conclusion
These results indicate the effectiveness of up-scale manufactured hUC-MSCs and hBM-MSCs in treating cartilage injuries, as demonstrated by repair tissue formation and a significantly better Wakitani score, compared to vehicle controls. The implanted MSCs did not appear to elicit an inflammatory response, further supporting their potential as an allogeneic treatment.
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