Mesenchymal Stem Cell Implantation in Knee Osteoarthritis: Midterm Outcomes and Survival Analysis in 467 Patients

Abstract

Background: A cell-based tissue engineering approach that uses mesenchymal stem cells (MSCs) has addressed the issue of articular cartilage repair in knees with osteoarthritis (OA). Purpose: To evaluate the midterm outcomes, analyze the survival rates, and identify the factors affecting the survival rate of MSC implantation to treat knee OA. Study Design: Case series; Level of evidence, 4. Methods: We retrospectively evaluated 467 patients (483 knees) who underwent MSC implantation on a fibrin glue scaffold for knee OA with a minimum 5-year follow-up. Clinical outcomes were determined based on the International Knee Documentation Committee (IKDC) and Tegner activity scale results measured preoperatively and during follow-up. Standard radiographs were evaluated using Kellgren-Lawrence grading. Statistical analyses were performed to determine the survival rate and the effect of different factors on the clinical outcomes. Results: The mean IKDC scores (baseline, 39.2 ± 7.2; 1 year, 66.6 ± 9.6; 3 years, 67.2 ± 9.9; 5 years, 66.1 ± 9.7; 9 years, 62.8 ± 8.5) and Tegner scores (baseline, 2.3 ± 1.0; 1 year, 3.4 ± 0.9; 3 years, 3.5 ± 0.9; 5 years, 3.4 ± 0.9; 9 years, 3.2 ± 0.9) were significantly improved until 3 years postoperatively and gradually decreased from 3- to 9-year follow-up ( P < .05 for all, except for Tegner score at 5 years vs 1 year [ P = .237]). Gradual deterioration of radiological outcomes according to the Kellgren-Lawrence grade was found during follow-up. Survival rates based on either a decrease in IKDC or an advancement of radiographic OA with Kellgren-Lawrence scores were 99.8%, 94.5%, and 74.5% at 5, 7, and 9 years, respectively. Based on multivariate analyses, older age and the presence of bipolar kissing lesion were associated with significantly worse outcomes ( P = .002 and .013, respectively), and a larger number of MSCs was associated with significantly better outcomes ( P < .001) after MSC implantation. Conclusion: MSC implantation provided encouraging outcomes with acceptable duration of symptom relief at midterm follow-up in patients with early knee OA. Patient age, presence of bipolar kissing lesion, and number of MSCs were independent factors associated with failure of MSC implantation.

Mesenchymal stem cell implantation provides short‐term clinical improvement and satisfactory cartilage restoration in patients with knee osteoarthritis but the evidence is limited: a systematic review performed by the early‐osteoarthritis group of ESSKA‐European knee associates section

“…To add to the ambiguity, the estimation of MSCs dosage may vary as some studies included the entire mononuclear cell count in dosage calculation, involving heterogenous population of cells such as platelet-rich plasma (PRP), autologous conditioned serum (ACS) apart from MSCs. Nonetheless, the current study suggests that clinical outcomes after MSCs' implantation are significantly influenced by MSCs' counts [18][19][20]. These findings concur with a recent meta-analysis, which found incremental improvement in VAS and KOOS with increasing dosage of MSCs injections at 12 months [23].…”

“…Initially, 2526 articles were identified. After evaluation for eligibility based on inclusion and exclusion criteria nine articles finally met the inclusion criteria [15, 16, 18–20, 25, 29, 30, 36].…”

“…Firstly, heterogeneity in terms of MSCs source and primary outcomes reported in the studies may have affected the analysis and data interpretation. Secondly, several included studies in this review were from South Korea, and from the same principal investigator which adds to bias [15,16,[18][19][20]. Thirdly, confounding effects may be present due to concurrent treatment (HTO) in four out of nine eligible studies.…”

“…The mean QoE was 12.8 for non-comparative studies [15,19,20,29,30] and 18.5 for comparative studies [18,36].…”

Equine umbilical cord mesenchymal stem cells demonstrate safety and efficacy in the treatment of canine osteoarthritis: a randomized placebo-controlled trial

“…Despite the fact that there are authors who claim that factors such as a younger age or male sex are associated with increased efficacy of MSCs, 47,48 in the present work, the effect of covariates (age, gender, OA grade, joint treated, severity) was evaluated, and none of them showed an effect on efficacy outcome (data not shown).…”