Bone marrow-derived mesenchymal stromal cells yield greater pain relief and tissue protection than umbilical cord tissue-derived cells in a surgically induced instability model of osteoarthritis.

OBJECTIVE

Intra-articular mesenchymal stromal cell (MSCs) injections are common to resolve osteoarthritic pain but have yielded inconsistent results in clinical trials in part due to variabilities across cell source and donors. The purpose of this study was to evaluate the relative potential of bone marrow (BM) and umbilical cord tissue (UCT) cell sources to slow post-traumatic osteoarthritis (PTOA) progression and relieve allodynia in male Lewis rats.

DESIGN

BM and UCT mesenchymal stromal cells (MSCs) from 4 human donors each were provided by our collaborators from a phase 3 multicenter clinical trial (MILES; NCT03818737). PTOA was induced in 3-month-old male Lewis rats using a medial meniscal transection (MMT). Sham surgeries were used as a control. MMT rats were either injected with saline or 1 × 106 MSCs at 3 weeks after surgery. Rats were evaluated for mechanical allodynia and gait. End-stage tissue health and synovial fluid inflammation were evaluated at 6 weeks post-surgery.

RESULTS

Evaluated BM-MSCs demonstrated superior therapeutic effects compared to UCT-MSCs. Only BM-MSC injections normalized tibial cartilage attenuation (effect size (95% Confidence Interval): -48.2 (-73.9 to -22.6) mgHA/ccm vs MMT/saline), while both cell types decreased tibial cartilage lesions (BM-MSC: -2.24 (-4.38 to -0.10) * 10-3 mm3 vs MMT/saline; UCT-MSC: -2.20 (-4.40 to -0.00) * 10-3 mm3 vs MMT/saline). Rats injected with UCT-MSCs displayed pathological increased tibial subchondral bone porosity (5.4 (2.5-8.3)% vs MMT/saline). Only BM-MSC injections reduced mechanical allodynia (5.36 (1.60-9.12) gf) and resolved shuffle step dysfunction. Both treatments resulted in distinct intra-articular inflammatory milieu. We observed variable efficacy among donors of both sources.

CONCLUSION

Although UCT-MSCs offer potential advantages in ontogenetic age and not requiring harvest, BM-MSCs demonstrated superior disease modification in a male rat PTOA model.