Regenerative Potential of Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis and Chondral Defects: A Systematic Review and Meta-analysis

Purpose To perform a systematic review and meta-analysis evaluating the effects of mesenchymal stem cells (MSCs) on cartilage regeneration and patient-reported pain and function. Methods A systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using a PRISMA checklist. The Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed (2008-2019), EMBASE (2008-2019), and MEDLINE (2008-2019) were queried in July 2019 for literature reporting use of stem cells to treat knee osteoarthritis or chondral defects. Data describing administered treatment, subject population, injection type, duration of follow-up, pain and functional outcomes, and radiographic and magnetic resonance imaging findings were extracted. Risk of bias was assessed using the Downs and Black scale. Meta-analyses adjusted for random effects were performed, calculating pooled effect sizes in terms of patient-reported pain and function, cartilage quality, and cartilage volume. Results Twenty-five studies with 439 subjects were identified. There was no significant difference in pain improvement between MSC treatment and controls (pooled standardized mean difference [SMD] = 0.23, P = .30). However, MSC treatment was significantly favored for functional improvement (SMD = 0.66, P < .001). There was improvement in cartilage volume after MSC treatment (SMD = 0.84, P < .001). Regarding cartilage quality, meta-analysis resulted in a small, nonsignificant effect size of 0.37 (95%, –0.03 to 0.77, P = .07). There was risk for potential bias among included studies, with 17 (68%) receiving either a grade of “poor” or “fair.” Conclusions The pooled SMD from meta-analyses showed statistically significant effects of MSC on self-reported physical function but not self-reported pain. MSCs provided functional benefit only in patients who underwent concomitant surgery. However, this must be interpreted with caution, as there was substantial variability in MSC composition and mode of delivery. MSC treatment provided significant improvement in cartilage volume but not cartilage quality. Preliminary data regarding therapeutic properties of MSC treatment suggest significant heterogeneity in the current literature, and risk of bias is not negligible. Level of Evidence II, Systematic Review and Meta-analysis To perform a systematic review and meta-analysis evaluating the effects of mesenchymal stem cells (MSCs) on cartilage regeneration and patient-reported pain and function. A systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using a PRISMA checklist. The Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed (2008-2019), EMBASE (2008-2019), and MEDLINE (2008-2019) were queried in July 2019 for literature reporting use of stem cells to treat knee osteoarthritis or chondral defects. Data describing administered treatment, subject population, injection type, duration of follow-up, pain and functional outcomes, and radiographic and magnetic resonance imaging findings were extracted. Risk of bias was assessed using the Downs and Black scale. Meta-analyses adjusted for random effects were performed, calculating pooled effect sizes in terms of patient-reported pain and function, cartilage quality, and cartilage volume. Twenty-five studies with 439 subjects were identified. There was no significant difference in pain improvement between MSC treatment and controls (pooled standardized mean difference [SMD] = 0.23, P = .30). However, MSC treatment was significantly favored for functional improvement (SMD = 0.66, P < .001). There was improvement in cartilage volume after MSC treatment (SMD = 0.84, P < .001). Regarding cartilage quality, meta-analysis resulted in a small, nonsignificant effect size of 0.37 (95%, –0.03 to 0.77, P = .07). There was risk for potential bias among included studies, with 17 (68%) receiving either a grade of “poor” or “fair.” The pooled SMD from meta-analyses showed statistically significant effects of MSC on self-reported physical function but not self-reported pain. MSCs provided functional benefit only in patients who underwent concomitant surgery. However, this must be interpreted with caution, as there was substantial variability in MSC composition and mode of delivery. MSC treatment provided significant improvement in cartilage volume but not cartilage quality. Preliminary data regarding therapeutic properties of MSC treatment suggest significant heterogeneity in the current literature, and risk of bias is not negligible.