Mesenchymal stem cell therapy for radiation-induced xerostomia: a systematic review and network meta-analysis

Radiation-induced xerostomia (RIX) is a frequent, debilitating complication of head and neck radiotherapy for cancer. Preclinical studies suggest that mesenchymal stem cells (MSCs) may protect and regenerate salivary glands, but clinical evidence remains fragmented. This study evaluates the safety and efficacy of MSC therapy for RIX patients.

Comprehensive searches of PubMed, Wiley Online Library, Cochrane, and CNKI were conducted up to July 2025 to identify relevant clinical studies. Two investigators independently screened records. A total of seven trials (n = 360 participants) were included. Meta-analyses were conducted using RevMan 5.4 and R Studio, with unstimulated whole salivary flow rate (UWS) as the primary endpoint. Secondary endpoints included stimulated whole salivary flow rate (SWS), Xerostomia Questionnaire (XQ) scores, and serious adverse events (SAE). Meta-analyses were conducted using RevMan 5.4 and R 4.5.1, with UWS as the primary endpoint. Heterogeneity was assessed by I² and large-study effects by Egger's test. The protocol was registered on PROSPERO (CRD420250521958).

Pooled analysis of the seven trials showed a statistically significant but clinically negligible increase in UWS with MSCs compared to controls (WMD = 0.02 mL/min, 95% CI: 0.00 to 0.03, p = 0.04). No significant differences were found for SWS (WMD = - 0.12 mL/min, 95% CI - 0.28 to 0.04) or XQ scores (WMD = - 0.54, 95% CI - 1.96 to 0.88; p = 0.46). The risk of SAE was not significantly different between groups (OR = 1.96, 95% CI 1.00-3.84, p = 0.05). Substantial heterogeneity was observed (I² >90%). Exploratory network meta-analysis suggested that bone marrow-derived MSCs (BMMSC) might outperform adipose-derived MSCs (ADMSC), but this finding is hypothesis-generating due to being based on a single BMMSC study.

MSC transplantationresults in a statistically significant but clinically marginal improvement in UWS for RIX, with no significant increase in SAE. The current evidence does not support the superiority of MSC therapy over conventional management. Future large-scale trials are required to determine if optimized MSC strategies can achieve clinically meaningful benefits.