Non-Cochrane · intervention · PM41857438
Treatment of Xerostomia with Mesenchymal Stem Cells - A Systematic Review and Meta-Analysis of Clinical Trials.
Hansen Joachim, Carlander Amanda-Louise Fenger, Jakobsen Kathrine Kronberg, et al. · Stem cell reviews and reports · 2026 · PubMed · doi:10.1007/s12015-026-11105-9
Findings
9 findings
| Population | ||||
|---|---|---|---|---|
| Patients with xerostomia or salivary hypofunction after head and neck radiotherapy or due to Sjogren's disease | Mesenchymal stem cell (MSC) injection into the salivary glands | Placebo (saline, saline with albumin, or DMSO) | Unstimulated whole salivary flow rate (UWS) Long term (6 months to 2 years; latest time point, 12 months) | MD 0.01 [-0.02, 0.05] GRADE not reported 2 studies · 150 participants |
| Patients with xerostomia or salivary hypofunction after head and neck radiotherapy or due to Sjogren's disease | Mesenchymal stem cell (MSC) injection into the salivary glands | Placebo (saline, saline with albumin, or DMSO) | Treatment-related adverse events (excluding pain during injection) Up to 12 months | RR 1.68 [1.4, 2.1] 12 % GRADE not reported 5 studies · 230 participants |
| Adults with xerostomia due to Sjogren's disease or head and neck radiotherapy | Mesenchymal stem cell (adipose-derived or bone marrow) injection into salivary glands | Placebo (saline, saline with albumin, or DMSO) | Treatment-related serious adverse events Follow-up 1 to 12 months · Intraglandular ultrasound-guided injection | Absolute risk 0 GRADE not reported 5 studies · 230 participants |
| Patients with xerostomia or salivary hypofunction after head and neck radiotherapy or due to Sjogren's disease | Mesenchymal stem cell (MSC) injection into the salivary glands | Placebo (saline, saline with albumin, or DMSO) | Stimulated whole salivary flow rate (SWS) Long term (6 months to 2 years; latest time point, 12 months) | MD -0.04 [-0.17, 0.10] GRADE not reported 2 studies · 150 participants |
| Patients with xerostomia or salivary hypofunction after head and neck radiotherapy or due to Sjogren's disease | Mesenchymal stem cell (MSC) injection into the salivary glands | Placebo (saline, saline with albumin, or DMSO) | Stimulated whole salivary flow rate (SWS) Short term (up to 6 months) | MD 0.05 [-0.32, 0.42] GRADE not reported 3 studies · 214 participants |
| Patients with xerostomia or salivary hypofunction after head and neck radiotherapy or due to Sjogren's disease | Mesenchymal stem cell (MSC) injection into the salivary glands | Placebo (saline, saline with albumin, or DMSO) | Unstimulated whole salivary flow rate (UWS) Short term (up to 6 months; time point closest to 4 months) | MD 0.06 [-0.05, 0.17] GRADE not reported 3 studies · 214 participants |
| Adults with xerostomia due to Sjogren's disease or head and neck radiotherapy | Mesenchymal stem cell (adipose-derived or bone marrow) injection into salivary glands | Placebo (saline, saline with albumin, or DMSO) | Treatment-related adverse events Follow-up 1 to 12 months · Intraglandular ultrasound-guided injection | RD 12 12 % GRADE not reported 5 studies · 230 participants |
| Patients with radiation-induced xerostomia | Mesenchymal stem cell (MSC) injection into the salivary glands | Placebo (saline, saline with albumin, or DMSO) | Unstimulated whole salivary flow rate (UWS) Short term (up to 6 months; about 4 months) · Radiation-induced xerostomia (Sjogren's disease trial excluded) | MD 0.03 [0.01, 0.05] GRADE not reported 2 studies · 150 participants |
| Adults with xerostomia due to Sjogren's disease or head and neck radiotherapy | Adipose-derived MSC (ASC) | Bone marrow derived MSC (BM-MSC) | Whole comparison (planned network meta-analysis of ASC vs BM-MSC) Intraglandular ultrasound-guided injection | no estimate extracted No studies found 0 studies |
Included primary studies 8
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Blitzer 2023 (MARSH) Marrow-Derived Autologous Stromal Cells for the Restoration of Salivary Hypofunction (MARSH): A pilot, first-in-human study of interferon… PMID:37589639 | 2023 | this review only | not stated | not extracted yet |
| Carlander 2025 (MESRIX-III 12-month follow-up) Long-term Effectiveness and Safety of Mesenchymal Stromal Cell Therapy for Radiation-Induced Hyposalivation in Head and Neck Cancer… PMID:39751638 | 2025 | this review only | Unstimulated whole salivary flow rate (UWS) | not extracted yet |
| Grønhøj 2018 (MESRIX) Safety and Efficacy of Mesenchymal Stem Cells for Radiation-Induced Xerostomia: A Randomized, Placebo-Controlled Phase 1/2 Trial (MESRIX). PMID:29678523 | 2018 | this review only | Unstimulated whole salivary flow rate (UWS) | not extracted yet |
| Jakobsen 2024 (MESRIX-II 12-month follow-up) Long-Term Outcome Following Treatment With Allogeneic Mesenchymal Stem/Stromal Cells for Radiation-Induced Hyposalivation and Xerostomia. PMID:38578768 | 2024 | this review only | not stated | not extracted yet |
| Jakobsen 2024 (MESRIX-III) Mesenchymal Stem/Stromal Cell Therapy for Radiation-Induced Xerostomia in Previous Head and Neck Cancer Patients: A Phase II Randomized,… PMID:38441659 | 2024 | this review only | Unstimulated whole salivary flow rate (UWS) | not extracted yet |
| Li 2023 Effect of adipose tissue-derived stem cells therapy on clinical response in patients with primary Sjogren's syndrome. PMID:37598237 | 2023 | this review only | Unstimulated whole salivary flow rate (UWS) | not extracted yet |
| Lynggaard 2022 (MESRIX 12-month follow-up) Long-term Safety of Treatment with Autologous Mesenchymal Stem Cells in Patients with Radiation-Induced Xerostomia: Primary Results of the… PMID:35486613 | 2022 | this review only | Unstimulated whole salivary flow rate (UWS) | not extracted yet |
| Lynggaard 2022 (MESRIX-II) Intraglandular Off-the-Shelf Allogeneic Mesenchymal Stem Cell Treatment in Patients with Radiation-Induced Xerostomia: A Safety Study… PMID:35435231 | 2022 | this review only | not stated | not extracted yet |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Humans with xerostomia due to Sjogren's disease or after head and neck radiotherapy | Radiation-induced xerostomia (4 trials) and Sjogren's disease (1 trial); 230 participants (126 MSC, 104 placebo) |
| Intervention | MSC treatment irrespective of administration route (original protocol: adipose-derived vs bone marrow derived MSC) | Allogeneic or autologous ASC (4 trials) and autologous BM-MSC (1 trial); ultrasound-guided intraglandular injection |
| Comparison | Placebo | Saline, saline with albumin or DMSO placebo (3 RCTs); no control group (2 trials) |
| Outcomes | Primary: unstimulated whole salivary flow rate; secondary: stimulated flow rate, PROMs, administration method, number of MSCs, drug-specific antibodies, adverse events | UWS and SWS (short and long term), PROMs (not pooled), adverse events, drug-specific antibodies, MSC number |
| Study designs | Clinical trials; RCTs pooled in meta-analysis | 3 RCTs and 2 non-randomized clinical trials (8 reports); 3 RCTs pooled |
| Timing | Short-term up to 6 months; long-term 6 months to 2 years | Follow-up 1 to 12 months |
AMSTAR 2 items
Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | Yes | Yes | yes |
| 2Protocol established before the reviewcritical | Yes | Yes | yes |
| 3Choice of study designs explained | No | No | yes |
| 4Comprehensive literature searchcritical | Partial Yes | Partial Yes | yes |
| 5Study selection in duplicate | No | No | yes |
| 6Data extraction in duplicate | Yes | Yes | yes |
| 7List of excluded studies with reasonscritical | No | No | yes |
| 8Included studies described in detail | Partial Yes | Partial Yes | yes |
| 9Risk of bias assessed satisfactorilycritical | RCT: Yes · NRSI: Yes | NRSI: Yes · RCT: Yes | no |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | RCT: Yes · NRSI: N/A | NRSI: N/A · RCT: Yes | no |
| 12Impact of risk of bias on the pooled results | Yes | No | no |
| 13Risk of bias accounted for in interpretationcritical | Yes | Yes | yes |
| 14Heterogeneity explained | Yes | Yes | yes |
| 15Publication bias investigatedcritical | Yes | Yes | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Low | Low | yes |