Introduction

Knee osteoarthritis (OA) is a progressive degenerative joint disorder characterized by cartilage breakdown and impaired joint function. 

Mesenchymal stem cells (MSCs) possess anti-inflammatory, immunomodulatory and regenerative and regenerative properties, making them a promising therapeutic option. However, robust clinical evidence, especially involving imaging biomarkers such as quantitative MRI, remains insufficient. 

Aim

To evaluate the efficacy and safety of a single intra-articular injection of allogeneic bone marrow–derived mesenchymal stem cells (BM-MSCs) in patients with knee OA (Kellgren–Lawrence (K–L) Grade I–IV), and to assess their potential disease-modifying effect using MRI-based cartilage analysis (baseline to 3 and 12 months). 

Patient Profile

The study enrolled  elderly patients with moderate-to-severe OA, with comparable baseline characteristics across groups, though symptom burden was slightly worse in the MSC arm.

 Methods

• Study Design: Randomized, double-blind, placebo-controlled trial.

Outcome Measures

• Primary outcomeswere changes in patient-reported outcome measures (PROMs).
  • VAS (pain)
  • Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
  • Knee Injury and Osteoarthritis Outcome Score (KOOS)
• Secondary outcomes
  • MRI T2 cartilage mapping
  • Bone turnover and inflammatory markers
• Safety: Adverse event monitoring 

Results

The study included a small but well-defined cohort of patients with knee OA, ensuring balanced allocation between treatment arms.

Table 1 : Baseline Characteristics

Parameter	Overall (n=24)
Mean age	67.5 ± 8.1 years
Female (%)	83.3%
BMI	25.0 ± 3.2 kg/m²
K–L Grade II–IV
II	37.5%
III	50.0%
IV	12.5%
Baseline VAS	72.3 ± 9.5
Baseline WOMAC	53.3 ± 20.0

 

 Patient-Reported Outcomes (PROMs) 

Table 2: VAS (Pain Score) Results

Timepoint	Control Group (MD, 95% CI)	MSC Group (MD, 95% CI)	P-value
3 months	−14.1 (−25.9 to −2.3)	−17.9 (−31.4 to −4.4)	0.640
6 months	−19.8 (−31.2 to −4.4)	−20.5 (−31.2 to −8.3)	0.915
9 months	−12.8 (−23.1 to −2.6)	−19.8 (−35.6 to −4.0)	0.412
12 months	−14.7 (−26.3 to −3.0)	−21.2 (−37.2 to −5.1)	0.469

 

Table 3: WOMAC Outcomes (All Domains)

Timepoint	WOMAC Total (Control vs MSC)	P-value	WOMAC Pain (Control vs MSC)	P-value	WOMAC Stiffness (Control vs MSC)	P-value	WOMAC Physical Function (Control vs MSC)	P-value
3 months	−8.1 vs −21.7	0.132	−1.6 vs −5.0	0.078	−1.6 vs −1.6	1.000	−4.9 vs −15.1	0.131
6 months	−10.8 vs −23.1	0.183	−2.3 vs −4.9	0.172	−1.8 vs −1.5	0.676	−6.8 vs −16.7	0.141
9 months	−4.8 vs −19.5	0.091	−0.1 vs −5.0	0.02	−1.3 vs −2.1	0.345	−3.5 vs −12.4	0.148
12 months	−7.1 vs −17.9	0.301	−0.6 vs −4.3	0.113	−1.3 vs −1.5	0.759	−5.3 vs −12.1	0.358

 

• Significant between-group difference observed only in KOOS pain at 9 months (P = 0.028) 
• Other KOOS domains demonstrated consistent numerical improvement with MSC therapy, 

Table 4 : KOOS Outcomes (All Domains)

Timepoint	KOOS Pain (Control vs MSC)	P-value	KOOS Symptom	P-value	KOOS ADL	P-value	KOOS Sport/Rec	P-value	KOOS QoL	P-value
3 months	11.6 vs 27.1	0.060	10.4 vs 23.4	0.158	10.0 vs 16.0	0.378	10.8 vs 27.3	0.081	7.8 vs 13.1	0.458
6 months	13.2 vs 29.5	0.086	14.9 vs 21.4	0.548	10.9 vs 22.1	0.168	15.0 vs 28.6	0.183	11.5 vs 14.2	0.676
9 months	7.2 vs 23.9	0.028	12.5 vs 19.8	0.409	7.5 vs 14.0	0.304	12.1 vs 27.3	0.111	9.4 vs 15.9	0.207
12 months	12.0 vs 23.2	0.266	15.5 vs 24.7	0.350	10.0 vs 15.0	0.430	15.8 vs 25.5	0.320	12.0 vs 11.9	0.995

 

MRI (T2 Mapping – Cartilage Degeneration) 

• Quantitative T2 mapping demonstrated a progressive increase in T2 values over time in both groups, indicative of cartilage compositional changes. 
• In the medial compartment, the control group showed a greater increase in mean T2 values from baseline to 12 months (38.83 to 44.04 ms), whereas the MSC group exhibited a comparatively attenuated increase (40.04 to 41.81 ms). 
• This difference between groups at 12 months was statistically significant (P = 0.013).
• No statistically significant differences were observed between groups in the lateral (P = 0.364) or patellofemoral compartments (P = 0.189)

Table 5: T2 values of knee cartilage across MSC and control groups

Timepoint	Control (T2 ms)	MSC (T2 ms)
Baseline	38.83	40.04
3 months	41.62	40.91
12 months	44.04	41.81

Inflammatory and Bone Turnover Markers

• MSC therapy demonstrated localized biological effects, reducing bone resorption without systemic inflammatory changes. 
• The mean ± standard deviation change in CTX-I levels from baseline in the MSC group was −0.1 ± 0.13 at 3 months, increasing to 0.05 ± 0.18 at 12 months. 
• A statistically significant difference in CTX-I levels between the MSC and control groups was observed only at 3 months (P = 0.049). 
• No statistically significant differences were noted between the groups for other inflammatory or bone turnover markers.

Safety Outcomes

• Adverse events were more common in the MSC group, occurring in 9 patients (75%), compared with 5 patients (45.5%) in the control group. 
• In the MSC group, these events were mainly related to the injection itself and typically included pain after the procedure, joint swelling, and some reduction in joint function.
• In the MSC group, Grade 1–3 AEs were observed, including mild pain, functional limitation requiring oral medication, and cases necessitating intra-articular corticosteroid injection. 
• In the control group, adverse events occurred in five patients but were not treatment-related
• All events in the MSC group resolved without hospitalization or study discontinuation.

Conclusion

A single intra-articular administration of allogeneic BM-MSCs was safe and effective for the clinical improvement of knee OA . The structural changes in knee OA evaluated using quantitative T2 cartilage mapping MRI showed a significant preventive effect on the degenerative progression of the cartilage at 12 months.

Reference

Cell Transplantation 2025; 34: 1–13.