Non-Cochrane · intervention · PM42158867
Efficacy and safety of stem cell therapy for dry eye syndrome in Sjögren's syndrome: a systematic review and meta-analysis.
Zhang Jizhong, Wang Wenshuang, Li Changyong · Frontiers in immunology · 2026 · PubMed · doi:10.3389/fimmu.2026.1834453
Findings
Population Patients with dry eye disease due to Sjogren's syndrome
39 findings
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | Pre-treatment baseline (within-group change) | Oxford score 4 weeks · Clinical trials in Sjogren's syndrome dry eye · Follow-up: 4 weeks | MD -0.70 [-1.30, -0.09] GRADE not reported 2 studies · 28 participants |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | Pre-treatment baseline (within-group change) | OSDI score 12 months · Clinical trials in Sjogren's syndrome dry eye · Follow-up: 12 months | MD -16.20 [-24.91, -7.50] GRADE not reported 2 studies · 25 participants |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | Pre-treatment baseline (within-group change) | Oxford score 12 months · Clinical trials in Sjogren's syndrome dry eye · Follow-up: 12 months | MD -0.17 [-1.06, 0.71] GRADE not reported 2 studies · 25 participants |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | Pre-treatment baseline (within-group change) | NIKBUT first 4 months · Clinical trials in Sjogren's syndrome dry eye · Follow-up: 4 months | MD 3.70 [2.13, 5.26] GRADE not reported 2 studies · 27 participants |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | Pre-treatment baseline (within-group change) | OSDI score All follow-up time points pooled · Clinical trials in Sjogren's syndrome dry eye | MD -15.10 [-18.65, -11.56] GRADE not reported 4 studies · 93 participants |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | Pre-treatment baseline (within-group change) | NIKBUT first 4 weeks · Clinical trials in Sjogren's syndrome dry eye · Follow-up: 4 weeks | MD 3.66 [-1.51, 8.82] GRADE not reported 2 studies · 28 participants |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | Pre-treatment baseline (within-group change) | Oxford score 2 weeks · Clinical trials in Sjogren's syndrome dry eye · Follow-up: 2 weeks | MD -1.00 [-1.62, -0.38] GRADE not reported 2 studies · 13 participants |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | Pre-treatment baseline (within-group change) | Schirmer test score All follow-up time points pooled · Clinical trials in Sjogren's syndrome dry eye | MD 3.87 [1.93, 5.81] GRADE not reported 4 studies · 93 participants |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | Pre-treatment baseline (within-group change) | Schirmer test score 4 months · Clinical trials in Sjogren's syndrome dry eye · Follow-up: 4 months | MD 3.52 [1.66, 5.38] GRADE not reported 2 studies · 27 participants |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | Pre-treatment baseline (within-group change) | NIKBUT first 2 weeks · Clinical trials in Sjogren's syndrome dry eye · Follow-up: 2 weeks | MD 3.48 [1.80, 5.16] GRADE not reported 2 studies · 13 participants |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | Pre-treatment baseline (within-group change) | Schirmer test score 2 weeks · Clinical trials in Sjogren's syndrome dry eye · Follow-up: 2 weeks | MD 8.76 [0.58, 16.94] GRADE not reported 2 studies · 13 participants |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | Pre-treatment baseline (within-group change) | OSDI score 4 weeks · Clinical trials in Sjogren's syndrome dry eye · Follow-up: 4 weeks | MD -12.89 [-19.49, -6.29] GRADE not reported 2 studies · 28 participants |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | Pre-treatment baseline (within-group change) | Schirmer test score 12 months · Clinical trials in Sjogren's syndrome dry eye · Follow-up: 12 months | MD 5.10 [0.24, 9.96] GRADE not reported 2 studies · 25 participants |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | Pre-treatment baseline (within-group change) | OSDI score 2 weeks · Clinical trials in Sjogren's syndrome dry eye · Follow-up: 2 weeks | MD -14.58 [-21.22, -7.95] GRADE not reported 2 studies · 13 participants |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | Pre-treatment baseline (within-group change) | Schirmer test score 4 weeks · Clinical trials in Sjogren's syndrome dry eye · Follow-up: 4 weeks | MD 1.16 [-1.71, 4.02] GRADE not reported 2 studies · 28 participants |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | Pre-treatment baseline (within-group change) | Oxford score 4 months · Clinical trials in Sjogren's syndrome dry eye · Follow-up: 4 months | MD 1.10 [0.55, 1.65] GRADE not reported 2 studies · 27 participants |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | Pre-treatment baseline (within-group change) | NIKBUT first All follow-up time points pooled · Clinical trials in Sjogren's syndrome dry eye | MD 3.26 [2.17, 4.34] GRADE not reported 4 studies · 93 participants |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | Pre-treatment baseline (within-group change) | Oxford score All follow-up time points pooled · Clinical trials in Sjogren's syndrome dry eye | MD -0.20 [-0.85, 0.45] GRADE not reported 4 studies · 93 participants |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | Pre-treatment baseline (within-group change) | NIKBUT first 12 months · Clinical trials in Sjogren's syndrome dry eye · Follow-up: 12 months | MD 2.70 [0.27, 5.13] GRADE not reported 2 studies · 25 participants |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | Pre-treatment baseline (within-group change) | OSDI score 4 months · Clinical trials in Sjogren's syndrome dry eye · Follow-up: 4 months | MD -19.77 [-28.16, -11.39] GRADE not reported 2 studies · 27 participants |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | No comparator (single-group incidence) | Periorbital edema (adverse event) During treatment · Clinical trials in Sjogren's syndrome dry eye · Time point: During treatment | Single-group rate 0.49 [0.32, 0.65] GRADE not reported 3 studies |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | No comparator (single-group incidence) | Blurred vision (adverse event) 1 week · Clinical trials in Sjogren's syndrome dry eye · Time point: 1 week | Single-group rate 0.12 [0.01, 0.23] GRADE not reported 3 studies |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | No comparator (single-group incidence) | Ocular discomfort (adverse event) All time points pooled · Clinical trials in Sjogren's syndrome dry eye | Single-group rate 0.41 [0.21, 0.62] GRADE not reported 3 studies |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | No comparator (single-group incidence) | Periorbital paresthesia (adverse event) During treatment · Clinical trials in Sjogren's syndrome dry eye · Time point: During treatment | Single-group rate 0.15 [-0.04, 0.35] GRADE not reported 2 studies |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | No comparator (single-group incidence) | Ocular discomfort (adverse event) 4 months · Clinical trials in Sjogren's syndrome dry eye · Time point: 4 months | Single-group rate 0.31 [0.06, 0.56] GRADE not reported 2 studies |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | No comparator (single-group incidence) | Periorbital edema (adverse event) 4 months · Clinical trials in Sjogren's syndrome dry eye · Time point: 4 months | Single-group rate 0.29 [-0.04, 0.62] GRADE not reported 1 study |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | No comparator (single-group incidence) | Ocular discomfort (adverse event) 1 week · Clinical trials in Sjogren's syndrome dry eye · Time point: 1 week | Single-group rate 0.60 [0.24, 0.95] GRADE not reported 3 studies |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | No comparator (single-group incidence) | Pain at injection site (adverse event) During treatment · Clinical trials in Sjogren's syndrome dry eye · Time point: During treatment | Single-group rate 0.30 [0.06, 0.54] GRADE not reported 3 studies |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | No comparator (single-group incidence) | Pain at injection site (adverse event) 1 week · Clinical trials in Sjogren's syndrome dry eye · Time point: 1 week | Single-group rate 0.36 [0.20, 0.52] GRADE not reported 3 studies |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | No comparator (single-group incidence) | Blurred vision (adverse event) During treatment · Clinical trials in Sjogren's syndrome dry eye · Time point: During treatment | Single-group rate 0.21 [-0.07, 0.50] GRADE not reported 3 studies |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | No comparator (single-group incidence) | Pain at injection site (adverse event) All time points pooled · Clinical trials in Sjogren's syndrome dry eye | Single-group rate 0.27 [0.16, 0.38] GRADE not reported 3 studies |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | No comparator (single-group incidence) | Ocular discomfort (adverse event) 4 weeks · Clinical trials in Sjogren's syndrome dry eye · Time point: 4 weeks | Single-group rate 0.16 [-0.04, 0.35] GRADE not reported 3 studies |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | No comparator (single-group incidence) | Periorbital edema (adverse event) 4 weeks · Clinical trials in Sjogren's syndrome dry eye · Time point: 4 weeks | Single-group rate 0.14 [-0.11, 0.39] GRADE not reported 1 study |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | No comparator (single-group incidence) | Pain at injection site (adverse event) 4 weeks · Clinical trials in Sjogren's syndrome dry eye · Time point: 4 weeks | Single-group rate 0.14 [-0.11, 0.39] GRADE not reported 1 study |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | No comparator (single-group incidence) | Blurred vision (adverse event) All time points pooled · Clinical trials in Sjogren's syndrome dry eye | Single-group rate 0.12 [0.02, 0.21] GRADE not reported 3 studies |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | No comparator (single-group incidence) | Ocular discomfort (adverse event) During treatment · Clinical trials in Sjogren's syndrome dry eye · Time point: During treatment | Single-group rate 0.65 [0.43, 0.87] GRADE not reported 1 study |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | No comparator (single-group incidence) | Periorbital edema (adverse event) All time points pooled · Clinical trials in Sjogren's syndrome dry eye | Single-group rate 0.46 [0.24, 0.67] GRADE not reported 3 studies |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | No comparator (single-group incidence) | Periorbital edema (adverse event) 1 week · Clinical trials in Sjogren's syndrome dry eye · Time point: 1 week | Single-group rate 0.59 [0.17, 1.01] GRADE not reported 3 studies |
| Stem cell therapy (mesenchymal or adipose-derived stem cells) | No comparator (single-group incidence) | Periorbital paresthesia (adverse event) All time points pooled · Clinical trials in Sjogren's syndrome dry eye | Single-group rate 0.15 [-0.04, 0.35] GRADE not reported 2 studies |
Included primary studies 5
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Habibi 2025 Efficacy of topical mesenchymal stem cell exosome in Sjögren's syndrome-related dry eye: a randomized clinical trial. PMID:40394561 | 2025 | this review only | not stated | not extracted yet |
| Mohammadpour 2025 Therapeutic Potential of Adipose-Derived Mesenchymal Stem Cells Transplantation into the Lacrimal Gland in Patients with Sjögren Syndrome. PMID:41297530 | 2026 | this review only | not stated | not extracted yet |
| Moller-Hansen 2021 Safety and feasibility of mesenchymal stem cell therapy in patients with aqueous deficient dry eye disease. PMID:33253910 | 2021 | this review only | not stated | not extracted yet |
| Moller-Hansen 2024 Allogeneic mesenchymal stem cell therapy for dry eye disease in patients with Sjögren's syndrome: A randomized clinical trial. PMID:38049032 | 2024 | this review only | not stated | not extracted yet |
| Zhang 2025 A first-in-human, prospective pilot trial of umbilical cord-derived mesenchymal stem cell eye drops therapy for patients with refractory… PMID:40269970 | 2025 | this review only | not stated | not extracted yet |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Individuals with dry eye syndrome caused by Sjögren's syndrome; no restriction on age, gender or ethnicity | Sjögren's syndrome-associated or refractory dry eye (n=114) |
| Intervention | Stem cell therapy (e.g. mesenchymal stem cells) | Allogeneic or autologous adipose-derived stem cells (injection) and umbilical cord MSCs or MSC exosomes (eye drops) |
| Comparison | Placebo or other treatments | Pre-treatment baseline (within-group change); placebo arms in 2 RCTs not used as comparator |
| Outcomes | OSDI score (primary); NIKBUT first, Oxford score, Schirmer test score; adverse events (ocular discomfort, injection site pain, periorbital oedema, periorbital paraesthesia, blurred vision) | OSDI, NIKBUT first, Oxford score, Schirmer test; pain at injection site, ocular discomfort, periorbital oedema, blurred vision, periorbital paresthesia |
| Study designs | Randomised controlled trials (double-blind or triple-blind) and self-controlled clinical trials | 2 randomised trials, 3 open-label self-controlled trials (n=5) |
| Timing | Minimum follow-up 3 months; time points 2 weeks, 4 weeks, 4 months, 12 months | Follow-up 3 to 12 months; time points 2 weeks, 4 weeks, 4 months, 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 | Partial Yes | Partial Yes | yes |
| 3Choice of study designs explained | No | No | yes |
| 4Comprehensive literature searchcritical | Partial Yes | Partial Yes | yes |
| 5Study selection in duplicate | Yes | Yes | yes |
| 6Data extraction in duplicate | No | No | 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: Partial Yes | NRSI: No · RCT: Yes | no |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | RCT: No · NRSI: No | NRSI: No · RCT: No | no |
| 12Impact of risk of bias on the pooled results | No | No | yes |
| 13Risk of bias accounted for in interpretationcritical | Yes | Yes | yes |
| 14Heterogeneity explained | Yes | Yes | yes |
| 15Publication bias investigatedcritical | No | No | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Critically Low | Critically Low | yes |