Non-Cochrane · intervention · PM42338052
Therapeutic efficacy of mesenchymal stem cells in periodontal regeneration: a systematic review and meta-analysis of clinical trials.
Ridho Fiki Muhammad, Irmawati Anis, Labib Raed, et al. · Journal of Yeungnam medical science · 2026 · PubMed · doi:10.12701/jyms.2026.43.42
Findings
109 findings
| Population | ||||
|---|---|---|---|---|
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Gingival recession (GR) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Apatzidou 2021 B | MD -0.22 [-0.43, -0.01] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Probing pocket depth (PPD) 6 to 12 months · Periodontal intrabony defects · MSC type: orally derived | MD -0.53 [-1.02, -0.04] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Probing pocket depth (PPD) 6 to 12 months · Periodontal intrabony defects · Study design: split-mouth | MD -0.51 [-0.73, -0.29] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Probing pocket depth (PPD) <=6 months · Periodontal intrabony defects · Follow-up: <=6 months | MD -0.51 [-0.90, -0.11] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Clinical attachment level (CAL) 6 to 12 months · Periodontal intrabony defects · MSC type: orally derived | MD -0.71 [-0.96, -0.45] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Clinical attachment level (CAL) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Chanreiphy 2025 C | MD -0.81 [-1.04, -0.58] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Clinical attachment level (CAL) >6 months · Periodontal intrabony defects · Follow-up: >6 months | MD -0.58 [-0.98, -0.19] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Gingival recession (GR) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Apatzidou et al. (2021) C | MD -0.21 [-0.41, -0.01] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Probing pocket depth (PPD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Sanchez 2020 B | MD -0.52 [-0.85, -0.19] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Clinical attachment level (CAL) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Ferrarotti et al. (2018) B | MD -0.73 [-0.94, -0.52] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Probing pocket depth (PPD) 6 to 12 months · Periodontal intrabony defects · MSC type: non-orally derived | MD -0.55 [-0.84, -0.25] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Intrabony defect depth (IBD) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Sreeparvathy et al. (2024) A | MD -1.08 [-1.59, -0.56] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Clinical attachment level (CAL) 6 to 12 months · Periodontal intrabony defects | MD -0.75 [-0.95, -0.54] High 10 studies |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Clinical attachment level (CAL) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Sreeparvathy et al. (2024) A | MD -0.74 [-0.95, -0.52] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Clinical attachment level (CAL) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Chanreiphy et al. (2025) A | MD -0.73 [-0.95, -0.51] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Probing pocket depth (PPD) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Chanreiphy et al. (2025) B | MD -0.52 [-0.86, -0.17] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Gingival recession (GR) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Chen et al. (2016) 1 | MD -0.17 [-0.38, 0.04] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Intrabony defect depth (IBD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Dhote 2015 | MD -1.02 [-1.57, -0.46] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | CEJ to base of defect (CEJ-BD) 6 to 12 months · Periodontal intrabony defects | MD -0.49 [-0.95, -0.02] Moderate Downgraded: inconsistency 3 studies |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Gingival recession (GR) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Liu et al. (2025) B1 | MD -0.18 [-0.38, 0.01] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Probing pocket depth (PPD) 6 to 12 months · Periodontal intrabony defects | MD -0.51 [-0.84, -0.19] Moderate Downgraded: inconsistency 10 studies |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Probing pocket depth (PPD) 6 to 12 months · Periodontal intrabony defects · Study design: parallel-arm | MD -0.71 [-1.26, -0.15] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Probing pocket depth (PPD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Sreeparvathy 2024 B | MD -0.51 [-0.85, -0.16] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Clinical attachment level (CAL) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Liu et al. (2025) A1 | MD -0.75 [-0.96, -0.54] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Probing pocket depth (PPD) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Apatzidou et al. (2021) B | MD -0.53 [-0.86, -0.20] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Clinical attachment level (CAL) 6 to 12 months follow-up · Study design: Split-mouth | MD -0.71 [-0.96, -0.45] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Gingival recession (GR) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Ferrarotti et al. (2018) B | MD -0.19 [-0.39, 0.01] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Clinical attachment level (CAL) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Chanreiphy 2025 B | MD -0.84 [-1.07, -0.62] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Intrabony defect depth (IBD) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Tobita et al. (2026) B | MD -1.04 [-1.58, -0.49] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Probing pocket depth (PPD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Sreeparvathy 2024 A | MD -0.53 [-0.87, -0.19] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Intrabony defect depth (IBD) 6 to 12 months · Periodontal intrabony defects · MSC type: orally derived | MD -0.87 [-1.75, 0.01] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Gingival recession (GR) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Liu et al. (2025) A2 | MD -0.20 [-0.40, 0.00] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Clinical attachment level (CAL) 6 to 12 months · Periodontal intrabony defects · Study design: parallel-arm | MD -0.89 [-1.30, -0.47] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Intrabony defect depth (IBD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Liu 2025 A2 | MD -1.20 [-1.72, -0.69] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Clinical attachment level (CAL) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Abdal-Wahab 2020 | MD -0.69 [-0.90, -0.48] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Probing pocket depth (PPD) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Tobita et al. (2026) A | MD -0.51 [-0.84, -0.18] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Probing pocket depth (PPD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Ferrarotti 2018 B | MD -0.47 [-0.79, -0.15] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Gingival recession (GR) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Liu et al. (2025) B2 | MD -0.18 [-0.38, 0.02] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Clinical attachment level (CAL) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Liu et al. (2025) A2 | MD -0.75 [-0.96, -0.54] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Probing pocket depth (PPD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Abdal-Wahab 2020 | MD -0.40 [-0.66, -0.14] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Gingival recession (GR) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Chen et al. (2016) 2 | MD -0.19 [-0.39, 0.02] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Gingival recession (GR) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Sánchez et al. (2020) A | MD -0.19 [-0.39, 0.00] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Probing pocket depth (PPD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Sanchez 2020 A | MD -0.55 [-0.87, -0.23] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Clinical attachment level (CAL) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Sanchez 2020 A | MD -0.77 [-0.98, -0.56] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | CEJ to base of defect (CEJ-BD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Apatzidou 2021 B | MD -0.38 [-0.84, 0.07] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Distance from cementoenamel junction to base of defect (CEJ-BD) 6 to 12 months follow-up · MSC type: Non-orally derived | MD -1.44 [-2.08, -0.81] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Clinical attachment level (CAL) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Chen et al. (2016) | MD -0.75 [-0.97, -0.54] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | CEJ to base of defect (CEJ-BD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Chen 2016 C | MD -0.52 [-1.06, 0.02] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Probing pocket depth (PPD) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Liu et al. (2025) B1 | MD -0.52 [-0.84, -0.19] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Clinical attachment level (CAL) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Tobita et al. (2026) B | MD -0.75 [-0.96, -0.54] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Gingival recession (GR) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Apatzidou et al. (2021) A | MD -0.19 [-0.39, 0.01] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Gingival recession (GR) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Liu et al. (2025) A1 | MD -0.19 [-0.39, 0.01] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Gingival recession (GR) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Sanchez 2020 B | MD -0.18 [-0.38, 0.01] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Clinical attachment level (CAL) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Sanchez 2020 B | MD -0.72 [-0.93, -0.51] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Probing pocket depth (PPD) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Ferrarotti et al. (2018) A | MD -0.46 [-0.78, -0.14] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | CEJ to base of defect (CEJ-BD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Chen 2016 B | MD -0.50 [-1.04, 0.04] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Intrabony defect depth (IBD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Ferrarotti 2018 A | MD -0.98 [-1.49, -0.46] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Intrabony defect depth (IBD) 6 to 12 months · Periodontal intrabony defects · Study design: parallel-arm | MD -0.98 [-1.54, -0.43] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Probing pocket depth (PPD) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Liu et al. (2025) A1 | MD -0.52 [-0.84, -0.20] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Probing pocket depth (PPD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Chen 2016 2 | MD -0.60 [-0.90, -0.30] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Probing pocket depth (PPD) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Liu et al. (2025) B2 | MD -0.52 [-0.84, -0.20] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | CEJ to base of defect (CEJ-BD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Chanreiphy 2025 B | MD -0.62 [-1.14, -0.09] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Probing pocket depth (PPD) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Chanreiphy et al. (2025) C | MD -0.53 [-0.87, -0.18] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Clinical attachment level (CAL) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Sreeparvathy 2024 B | MD -0.73 [-0.95, -0.51] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | CEJ to base of defect (CEJ-BD) <=6 months · Periodontal intrabony defects · Follow-up: <=6 months | MD -0.54 [-1.18, 0.11] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Intrabony defect depth (IBD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Apatzidou 2021 B | MD -1.12 [-1.66, -0.57] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | CEJ to base of defect (CEJ-BD) 6 to 12 months · Periodontal intrabony defects · Study design: split-mouth | MD -0.12 [-0.42, 0.17] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Probing pocket depth (PPD) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Liu et al. (2025) A2 | MD -0.52 [-0.84, -0.20] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Gingival recession (GR) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Ferrarotti 2018 A | MD -0.17 [-0.37, 0.04] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Intrabony defect depth (IBD) <=6 months · Periodontal intrabony defects · Follow-up: <=6 months | MD -0.93 [-1.49, -0.36] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | CEJ to base of defect (CEJ-BD) 6 to 12 months · Periodontal intrabony defects · Study design: parallel-arm | MD -1.44 [-2.08, -0.81] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Intrabony defect depth (IBD) 6 to 12 months · Periodontal intrabony defects · MSC type: non-orally derived | MD -1.36 [-1.84, -0.87] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Intrabony defect depth (IBD) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Apatzidou et al. (2021) A | MD -1.15 [-1.70, -0.61] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | CEJ to base of defect (CEJ-BD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Chanreiphy 2025 A | MD -0.57 [-1.15, 0.01] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Intrabony defect depth (IBD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Ferrarotti 2018 B | MD -0.96 [-1.47, -0.46] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Intrabony defect depth (IBD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Sreeparvathy 2024 B | MD -1.07 [-1.58, -0.56] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | CEJ to base of defect (CEJ-BD) 6 to 12 months · Periodontal intrabony defects · MSC type: orally derived | MD -0.15 [-0.41, 0.12] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | CEJ to base of defect (CEJ-BD) >6 months · Periodontal intrabony defects · Follow-up: >6 months | MD -0.46 [-1.30, 0.39] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Intrabony defect depth (IBD) 6 to 12 months · Periodontal intrabony defects | MD -1.09 [-1.60, -0.57] Moderate Downgraded: inconsistency 6 studies |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Gingival recession (GR) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Dhote 2015 | MD -0.09 [-0.29, 0.12] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Probing pocket depth (PPD) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Tobita et al. (2026) B | MD -0.51 [-0.84, -0.18] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Intrabony defect depth (IBD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Liu 2025 B2 | MD -1.18 [-1.72, -0.65] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Intrabony defect depth (IBD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Liu 2025 B1 | MD -1.15 [-1.69, -0.61] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Probing pocket depth (PPD) >6 months · Periodontal intrabony defects · Follow-up: >6 months | MD -0.48 [-0.88, -0.09] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Clinical attachment level (CAL) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Dhote 2015 | MD -0.68 [-0.89, -0.46] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Clinical attachment level (CAL) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Apatzidou et al. (2021) B | MD -0.77 [-0.98, -0.56] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Clinical attachment level (CAL) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Apatzidou et al. (2021) A | MD -0.76 [-0.97, -0.55] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Intrabony defect depth (IBD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Tobita 2026 C | MD -1.04 [-1.59, -0.50] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Clinical attachment level (CAL) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Liu et al. (2025) B2 | MD -0.75 [-0.96, -0.54] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Probing pocket depth (PPD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Dhote 2015 | MD -0.48 [-0.82, -0.15] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Clinical attachment level (CAL) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Ferrarotti et al. (2018) A | MD -0.71 [-0.92, -0.50] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Clinical attachment level (CAL) 6 to 12 months · Periodontal intrabony defects · MSC type: non-orally derived | MD -0.83 [-1.21, -0.46] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Gingival recession (GR) 6 to 12 months · Periodontal intrabony defects | MD -0.18 [-0.38, 0.01] Moderate Downgraded: imprecision 6 studies |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Intrabony defect depth (IBD) 6 to 12 months · Periodontal intrabony defects · Study design: split-mouth | MD -5.22 [-12.50, 2.07] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Intrabony defect depth (IBD) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Liu et al. (2025) A1 | MD -1.17 [-1.71, -0.64] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Probing pocket depth (PPD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Chen 2016 1 | MD -0.55 [-0.89, -0.21] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Probing pocket depth (PPD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Tobita 2026 C | MD -0.51 [-0.83, -0.18] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Clinical attachment level (CAL) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Tobita et al. (2026) A | MD -0.75 [-0.96, -0.54] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Intrabony defect depth (IBD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Tobita 2026 A | MD -1.07 [-1.63, -0.51] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Clinical attachment level (CAL) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Liu et al. (2025) B1 | MD -0.75 [-0.96, -0.54] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | CEJ to base of defect (CEJ-BD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Apatzidou 2021 A | MD -0.20 [-0.46, 0.06] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Clinical attachment level (CAL) <=6 months · Periodontal intrabony defects · Follow-up: <=6 months | MD -0.81 [-1.05, -0.56] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Clinical attachment level (CAL) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Apatzidou et al. (2021) C | MD -0.76 [-0.97, -0.55] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Probing pocket depth (PPD) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Apatzidou et al. (2021) A | MD -0.54 [-0.86, -0.21] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Probing pocket depth (PPD) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Chanreiphy et al. (2025) A | MD -0.52 [-0.86, -0.17] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Clinical attachment level (CAL) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Tobita 2026 C | MD -0.75 [-0.96, -0.54] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV or moderate-severe periodontitis with periodontal (intrabony) defects after phase I therapy | Mesenchymal stem cell (MSC) based therapy | Cell-free control treatment (same scaffold, surgery or other treatment without stem cells) | Probing pocket depth (PPD) 6 to 12 months follow-up · Leave-one-out sensitivity analysis omitting Apatzidou et al. (2021) C | MD -0.53 [-0.86, -0.20] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | CEJ to base of defect (CEJ-BD) 6 to 12 months · Periodontal intrabony defects · Sensitivity: leave-one-out, omitting Chen 2016 A | MD -0.56 [-1.08, -0.04] GRADE not reported Studies not reported |
| Systemically healthy adults with stage III-IV (moderate-severe) periodontitis and periodontal intrabony defects after phase I therapy | Mesenchymal stem cell-based therapy (with or without scaffolds) | Cell-free control treatment (scaffold, membrane, open flap debridement or other cell-free strategy) | Intrabony defect depth (IBD) >6 months · Periodontal intrabony defects · Follow-up: >6 months | MD -1.78 [-2.63, -0.92] GRADE not reported Studies not reported |
Included primary studies 18
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Ferrarotti 2018 Human intrabony defect regeneration with micrografts containing dental pulp stem cells: A randomized controlled clinical trial. PMID:29779220 | 2018 | 4 other reviews | not stated | not extracted yet |
| Chen 2016 Treatment of periodontal intrabony defects using autologous periodontal ligament stem cells: a randomized clinical trial. PMID:26895633 | 2016 | 3 other reviews | not stated | not extracted yet |
| Sánchez 2020 Periodontal regeneration using a xenogeneic bone substitute seeded with autologous periodontal ligament-derived mesenchymal stem cells: A… PMID:32946590 | 2020 | 3 other reviews | not stated | not extracted yet |
| Apatzidou 2021 A tissue-engineered biocomplex for periodontal reconstruction. A proof-of-principle randomized clinical study. PMID:33899259 | 2021 | 2 other reviews | not stated | not extracted yet |
| Abdal-Wahab 2020 Regenerative potential of cultured gingival fibroblasts in treatment of periodontal intrabony defects (randomized clinical and biochemical… PMID:32080858 | 2020 | 1 other review | not stated | not extracted yet |
| Apatzidou 2021 A tissue‐engineered biocomplex for periodontal reconstruction. A proof‐of‐principle randomized clinical study DOI:10.1111/jcpe.13474 | 2021 | 1 other review | not stated | not extracted yet |
| Ferrarotti 2018 Human intrabony defect regeneration with micrografts containing dental pulp stem cells: A randomized controlled clinical trial DOI:10.1111/jcpe.12931 | 2018 | 1 other review | not stated | not extracted yet |
| Liu 2025 Impact of allogeneic dental pulp stem cell injection on tissue regeneration in periodontitis: a multicenter randomized clinical trial. PMID:40739139 | 2025 | 1 other review | not stated | not extracted yet |
| Sreeparvathy 2024 Platelet Rich Fibrin Matrix (PRFM) and Peripheral Blood Mesenchymal Stem Cells (PBMSCs) in the management of intraosseous defects - A… DOI:10.1590/1678-7757-2023-0442 | 2024 | 1 other review | not stated | not extracted yet |
| Sreeparvathy 2024 Platelet Rich Fibrin Matrix (PRFM) and Peripheral Blood Mesenchymal Stem Cells (PBMSCs) in the management of intraosseous defects - A… PMID:39109750 | 2024 | 1 other review | not stated | not extracted yet |
| Abdal-Wahab 2020 Regenerative potential of cultured gingival fibroblasts in treatment of periodontal intrabony defects (randomized clinical and biochemical… DOI:10.1111/jre.12728 | 2020 | this review only | not stated | not extracted yet |
| Chanreiphy 2025 Evaluation of autologous periodontal stem cells niche in the treatment of periodontal intrabony defects: A split-mouth randomized… PMID:40636765 | 2025 | this review only | not stated | not extracted yet |
| Chen 2016 Treatment of periodontal intrabony defects using autologous periodontal ligament stem cells: a randomized clinical trial DOI:10.1186/s13287-016-0288-1 | 2016 | this review only | not stated | not extracted yet |
| Dhote 2015 Stem Cells Cultured on Beta Tricalcium Phosphate (β-TCP) in Combination with Recombinant Human Platelet-Derived Growth Factor - BB… PMID:27144828 | 2015 | this review only | not stated | not extracted yet |
| Liu 2025 Impact of allogeneic dental pulp stem cell injection on tissue regeneration in periodontitis: a multicenter randomized clinical trial DOI:10.1038/s41392-025-02320-w | 2025 | this review only | not stated | not extracted yet |
| Sanchez 2020 Periodontal regeneration using a xenogeneic bone substitute seeded with autologous periodontal ligament‐derived mesenchymal stem cells: A… DOI:10.1111/jcpe.13368 | 2020 | this review only | not stated | not extracted yet |
| Tobita 2026 Efficacy and safety of autologous adipose-derived stem cells combined with platelet-rich plasma for periodontal regeneration: a… DOI:10.1016/j.reth.2026.101062 | 2026 | this review only | not stated | not extracted yet |
| Tobita 2026 Efficacy and safety of autologous adipose-derived stem cells combined with platelet-rich plasma for periodontal regeneration: a… PMID:41624073 | 2026 | this review only | not stated | not extracted yet |
Overlap with other reviews
Reviews that include the same primary studies are not independent evidence. Shared counts match studies by PMID, DOI or NCT, and otherwise by author and year (a probable match). Only the non-Cochrane dental reviews have study lists, so overlap with Cochrane reviews is not counted yet.
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Systemically healthy adults with stage III-IV/moderate-severe periodontitis with periodontal defects who had at least phase I periodontal therapy | Patients aged 18 years or older with periodontitis and intrabony defects (n=276 patients in 10 RCTs) |
| Intervention | MSC-based therapy | MSC-based therapy: gingival, periodontal ligament, dental pulp (orally derived, 6 RCTs); bone marrow, umbilical cord, peripheral blood, adipose (non-orally derived, 4 RCTs) |
| Comparison | Another treatment strategy without stem cells (cell-free control) | Cell-free control: scaffold, graft, flap surgery or saline without stem cells (10 RCTs) |
| Outcomes | PPD; CAL; gingival recession; CEJ to base of defect; intrabony defect | PPD (n=10 trials); CAL (n=10); GR (n=6); CEJ-BD (n=3); IBD (n=6) |
| Study designs | RCTs published in English-language peer-reviewed journals | Ten RCTs: 3 split-mouth, 6 parallel-arm, 1 teeth as unit |
| Timing | Not specified | Follow-up 6 months (4 RCTs), 9 months (2 RCTs), 12 months (4 RCTs) |
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 | 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: N/A | NRSI: N/A · RCT: Yes | no |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | RCT: No · NRSI: N/A | NRSI: N/A · RCT: Yes | 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 | Yes | Yes | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Critically Low | Low | no |