Cytopeutics umbilical cord-derived mesenchymal stem cells are associated with earlier clinical improvement compared to bone marrow aspirate concentrate with scaffold in knee cartilage injury: A Phase 1 feasibility and Phase 2 randomized controlled trial.

INTRODUCTION

Despite advances in the development of mesenchymal stem cells (MSCs), the ultimate benefits of MSCs against current cell-based therapies are still limited. This study aimed to assess the safety, feasibility, and efficacy of Cytopeutics® umbilical cord-derived MSCs (Chondrocell-EX) in patients with knee cartilage injury.

MATERIALS AND

METHODS

The study was conducted in two parts: a phase I feasibility study (PI) followed by a phase II randomized controlled trial (PII). Both studies were approved by UKM Research Ethics Committee (PI: UKM PPI/111/8; PII: UKM PPI/111/8/JEP-2019-304). Six patients were involved in the PI study in which all patients received Chondrocell-EX and 28 patients in the following PII study, where 17 patients received Chondrocell-EX with Hyaluronic acid (HA) (Arm A) and 11 patients received commercially available cell-based therapy, which is Bone Marrow Aspirate Concentrate (BMAC) with Hyaluronic acid-based scaffold (HA-S) (Arm B). Safety was assessed based on the occurrence of adverse events, while clinical outcomes were assessed based on the Knee Injury and Osteoarthritis Outcome Score (KOOS) and Pain Visual Analog Scale (VAS). Second-look arthroscopy and histological assessment were performed to assess their structural outcomes at 12 months.

RESULTS

In the PI feasibility study, significant pain reduction began at 3 months, with mean VAS decreasing from 6.83 ± 0.98 at baseline to 4.83 ± 1.17 (p < 0.01), 3.00 ± 0.00 at 6 months (p < 0.01), and 1.83 ± 0.75 at 12 months (p < 0.01). In the PII study, Arm A (Chondrocell-EX + HA) demonstrated significant VAS improvements at all follow-up points compared to baseline (p < 0.001), whereas Arm B (BMAC + HA-S) showed significant reductions only from 3 months onward. After adjustment for baseline age and VAS, Arm A achieved significantly lower pain scores than Arm B at 6 months (2.56 ± 1.41 vs 3.09 ± 1.22; p = 0.015) and 12 months (2.27 ± 1.49 vs 2.50 ± 1.35; p = 0.043), indicating earlier and sustained pain relief with Chondrocell-EX injection. Functional outcomes mirrored pain improvements. In PI, KOOS scores improved significantly from 3 months, reaching 85.83 ± 11.87 at 12 months (p < 0.01). In PII, KOOS increased significantly in both arms (p < 0.001), but Arm A demonstrated earlier gains at 3 months and significantly higher adjusted KOOS scores than Arm B at 6 (p = 0.009) and 12 months (p = 0.037). In KOOS subdomains analysis, it showed significantly greater improvements in Arm A, particularly in symptoms and stiffness, activity of daily living (ADL), pain, sport and recreation, and quality of life (QoL) at key time points.

CONCLUSION

Chondrocell-EX+HA treatment is more convenient, feasible, and minimally invasive with the findings suggesting that it is associated with faster functional improvement and pain relief, along with demonstration of hyaline-like cartilage regeneration, compared to the BMAC+HA-S method.