Can Mesenchymal Stem Cells Improve Bone Regeneration in Maxillary Sinus Augmentation? A Systematic Review and Meta-Analysis

Background: Mesenchymal stem cells (MSCs) have shown promise in preclinical models for enhancing bone regeneration around dental implants. However, clinical evidence regarding their efficacy in maxillary sinus augmentation procedures for dental implants remains inconclusive. Objective: To evaluate the clinical effectiveness of MSC-based regenerative therapies compared to conventional grafting in maxillary sinus augmentation for implant placement. Methods: A systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and registered in PROSPERO (CRD42023488758). Electronic and gray literature searches were performed across six databases. Eligible studies included randomized clinical trials evaluating MSC-based bone regeneration in maxillary sinus lifts. Risk of bias (RoB) was assessed using the Cochrane RoB 2.0 tool, and certainty of evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. Meta-analyses were performed for implant success rate and bone formation outcomes. Results: Six randomized controlled trials (RCTs) were included, comprising 74 patients and 222 implants. Meta-analysis revealed no statistically significant difference in implant success rate between MSC and control groups (risk ratio [RR] = 0.98; 95% confidence interval [CI]: 0.94–1.03; p = 0.50; I² = 11.69%). For bone neoformation, continuous data favored the control group (standardized mean difference [SMD] = –0.83; 95% CI: –1.37 to –0.30; p = 0.002; I² = 0%; indicating a medium to large effect size that represents a clinically perceptible advantage in bone formation for the control interventions), while dichotomous outcomes showed no significant difference (RR = 1.11; 95% CI: 0.73–1.67; p = 0.62). Sensitivity analyses confirmed the robustness of findings. The certainty of evidence was rated as high for bone formation outcomes and moderate for implant success. Conclusions: MSC-based regenerative therapies do not appear to offer a significant clinical advantage over conventional grafting techniques in maxillary sinus augmentation. These results should be interpreted with caution, given the limited number of trials and clinical heterogeneity. Further well-designed studies are needed to validate their efficacy in implant-related bone regeneration.