Safety and Efficacy of Cultured/Noncultured Mesenchymal Stromal Cells without Concurrent Surgery for Knee Osteoarthritis: A Systematic Review of Randomized Controlled Trials

Abstract

The quantity of studies investigating mesenchymal stromal cells (MSCs) for knee osteoarthritis (OA) treatment is not restricted, unlike the amount of randomized controlled trials (RCTs) that can be found in the literature. MSCs demonstrate a promising potential for safe pain relief of OA, yet indeterminate conclusions prevail due to heterogeneous reporting and study design. By evaluating PubMed and ScienceDirect for RCTs that describe patient-reported outcome measures (PROMs) and adverse events (AEs), we investigate safety and efficacy of MSCs for knee OA unaccompanied by adjuvant surgical intervention. This systematic review is performed in alignment with preferred reported items for systematic reviews and meta-analyses guidelines. In addition to PROMs and AEs, we review included studies for stromal cell variants, follow-up, and imaging modalities, reporting our results in tables and text. Twelve studies that ranged from 1 wk to 4 yr and examined 428 patients and 856 knees met inclusion criteria. Six studies (50%) evaluated bone marrow MSCs, five (42%) evaluated adipose-derived MSCs, and one (8%) evaluated umbilical cord MSCs. All studies reported significant PROM improvement. Mean improvements in the visual analog scale and Western Ontario and McMaster Universities Arthritis Index, ranging from 0 to 40 and 10 to 32 points, respectively, were observed. Of 343 total patients, 135 (39%) experienced AEs. Whereas most AEs involved self-limiting knee swelling and pain, only three (0.8%) were severe enough to require overnight hospitalization. MSCs without adjuvant surgery offer a safe and efficacious conservative treatment option in knee OA patients by alleviating and decreasing pain for up to 12 mo. However, study limitations and contradictory findings require more evidence regarding cartilage repair.