TABLE 8.
Preclinical in vivo and clinical studies of hMSCs used as advanced therapy for atopic dermatitis in the last 5 years.
| PRECLINICAL IN VIVO STUDIES | |||||||||||
| Type of advanced therapy | Cells | Type of hMSC treatment evaluated | Disease models | Follow-up | References | ||||||
| Cell therapy | hUCB-MSCs | 1-hUCB-MSCs group: 2 × 106 cells injected intravenously on days 2, 9, 16 and 23. 2-Muramyl dipeptide – hUCB-MSCs (intravenous) group: 2 × 106 injected intravenously on days 2, 9, 16 and 23 previous administration of muramyl dipeptide. 3-Muramyl dipeptide – hUCB-MSCs (subcutaneous) group: 2 × 106 injected subcutaneously on days 2, 9, 16 and 23 previous administration of muramyl dipeptide. | Dermatophagoides farinae-induced murine atopic dermatitis model | 30 days | Kim et al., 2015 | ||||||
| hAT-MSCs | 1-hAT-MSCs (low) group: 2 × 105 cells injected intravenously 2-hAT-MSCs (high) group: 2 × 106 cells injected intravenously 3-Fibroblasts group: Human dermal fibroblasts injected intravenously | Dermatophagoides farinae-induced murine atopic dermatitis model | 14 days | Shin et al., 2017 | |||||||
| hAT-MSCs | 1-hAT-MSCs group: 106 cells injected intravenously on days 0 and 11 2-Fibroblasts group: Human dermal fibroblasts injected intravenously | Acetone and 2, 4-dinitrochlorobenzene (DNCB): olive oil mixture (4:1 vol/vol) induced atopic dermatitis | 24 days | Kim J.M. et al., 2018 | |||||||
| hUCB-MSCs | 1-hUCB-MSCs group: subcutaneous administration of 106 cells 2-MC-hUCB-MSCs primed group: subcutaneous administration of 106 cells primed with mast cells granules 3-Fibroblasts group: subcutaneous administration of 106 cells | 4% sodium dodecyl sulfate (SDS) and Dermatophagoides farinae extract induced atopic dermatitis | 14 days | Lee et al., 2019 | |||||||
| hWJ-MSCs | 1-hWJ-MSCs group: subcutaneous administration of 2 × 106 cells 2-hWJ-MSCs-poly I:C group: subcutaneous administration of 2 × 106 cells primed with poly I:C 3-hWJ-MSCs- IFN-γ group: subcutaneous administration of 2 × 106 cells primed with IFN-γ | Aspergillus fumigatus extract to induce atopic dermatitis | 5 days | Park et al., 2019 | |||||||
| Cell therapy and gene therapy | hUCB-MSCs | 1-hUCB-MSCs group: 2 × 106 cells injected subcutaneous on day 20, 28 and 42 and one time on day 56 after the development of atopic dermatitis 2-hUCB-MSCs transduced group: 2 × 106 superoxide dismutase 3 (SOD3) transduced cells injected subcutaneous on day 20, 28 and 42 and one time on day 56 after the development of atopic dermatitis | Ovalbumin – atopic dermatitis induced mouse model | 56 days | Sah et al., 2018 | ||||||
| hUCB-MSCs | 1-hUCB-MSCs group: subcutaneous injection of 2 × 106 cells 2-hUCB-MSCs transfected control group: subcutaneous injection of 2 × 106 cells transfected with siRNA control 3-hUCB-MSCs transfected siTGF-β group: subcutaneous injection of 2 × 106 cells transfected with siRNA targeting TGF-β | Dermatophagoides farina extract containing components of house dust mites to induce atopic dermatitis | 7 days | Park H.H. et al., 2020 | |||||||
| CLINICAL STUDIES | |||||||||||
| Type of advanced therapy | Cells | Type of clinical study | N (male/female) | Age (years)a | hMSC treatment | Safety (Treatment-related adverse events) | Indication | Effectivenessa | Follow-upa | References | |
| Cell therapy | Allogeneic hUCB-MSCs | Phase I/II Randomized Clinical Trial (Double Blind) | For safety:33 For efficacy: 25 (16/5) | For safety: 20–60 For efficacy: 28.63 (20–60) | Subcutaneous administration of hUCB-MSCs at two different doses (low dose; 2.5 × 107 cells or high dose; 5.0 × 107 cells) | Low dose: 12% of patients (1 event per patient) High dose: 56% patients (1.78 events per patient) | Moderate to severe Atopic Dermatitis (Severity Scoring for Atopic Dermatitis (SCORAD) > 20) | After 12 weeks, SCORAD value was reduced: Low dose: −28.04 ± 6.20% High dose: −49.97 ± 4.33% | 12 weeks | Kim et al., 2017 | |
| Autologous hMSCs (not defined) | Phase I Clinical Trial (Single Group Assignment- Open Label) | 13 | (19–70) | Two different doses of hMSCs administered by intravenous infusion: 1 × 108 cells or 3 × 108 cells | – | Moderate to Severe, Subacute and Chronic Atopic Dermatitis | – | 12 weeks | NCT02888704 (Safety and Efficacy of ADSTEM Inj. in Patients With Moderately Subacute and Chronic Atopic Dermatitis – Full Text View – ClinicalTrials.gov)2 | ||
| Autologous hMSCs (not defined) | Observational Study | 11 | (19–70) | Two different doses of hMSCs administered by intravenous infusion: 1 × 108 cells or 3 × 108 cells | – | Moderate to Severe, Subacute and Chronic Atopic Dermatitis | – | 60 months | NCT03252340 (Safety of ADSTEM Injection in Patients With Moderate to Severe Subacute and Chronic Atopic Dermatitis – Full Text View – ClinicalTrials.gov)4 | ||
| Allogeneic hBM-MSCs | Phase I/II Multicenter Randomized Clinical Trial (Parallel Assignment- Quadruple Blind) | 92 | Older than 19 | Three doses of 106 cells injected intravenously at weeks 0, 2 and 4 | – | Moderate to Severe Atopic Dermatitis | – | 24 weeks | NCT04179760 (Safety and Efficacy of SCM-AGH in Subjects With Moderate to Severe Atopic Dermatitis – Full Text View – ClinicalTrials. gov)3 | ||
| hAT-MSCs | Phase II Multicenter Randomized Clinical Trial (Parallel Assignment- Double Blind) | 118 | (19–70) | Two intravenous injections of 0.5 × 108 cells | – | Moderate to Severe, Subacute and Chronic Atopic Dermatitis | – | 16 weeks | NCT04137562 (Safety and Efficacy in Patients With Moderate to Severe Subacute and Chronic Atopic Dermatitis – Full Text View – ClinicalTrials. gov)1 | ||
aExpression of measures: mean ± standard deviation (range).
1Safety and Efficacy in Patients With Moderate to Severe Subacute and Chronic Atopic Dermatitis – Full Text View – ClinicalTrials.gov Available at: https://www.clinicaltrials.gov/ct2/show/NCT04137562?term=mesenchymal+stem+cells&recrs=abdefgh&cond=atopic+dermatitis&strd_s=01%2F01%2F2015&strd_e=12%2F31%2F2020&draw=2&rank=4 [Accessed January 21, 2021].
2Safety and Efficacy of ADSTEM Inj. in Patients With Moderately Subacute and Chronic Atopic Dermatitis – Full Text View – ClinicalTrials.gov Available at: https://www.clinicaltrials.gov/ct2/show/study/NCT02888704?term=mesenchymal+stem+cells&recrs=abdefgh&cond=atopic+dermatitis&strd_s=01%2F01%2F2015&strd_e=12%2F31%2F2020&draw=2&rank=1 [Accessed January 21, 2021].
3Safety and Efficacy of SCM-AGH in Subjects With Moderate to Severe Atopic Dermatitis – Full Text View – ClinicalTrials.gov Available at: https://www.clinicaltrials.gov/ct2/show/NCT04179760?term=mesenchymal+stem+cells&recrs=abdefgh&cond=atopic+dermatitis&strd_s=01%2F01%2F2015&strd_e=12%2F31%2F2020&draw=2&rank=3 [Accessed January 21, 2021].
4Safety of ADSTEM Injection in Patients With Moderate to Severe Subacute and Chronic Atopic Dermatitis – Full Text View – ClinicalTrials.gov Available at: https://www.clinicaltrials.gov/ct2/show/NCT03252340?term=mesenchymal+stem+cells&recrs=abdefgh&cond=atopic+dermatitis&strd_s=01%2F01%2F2015&strd_e=12%2F31%2F2020&draw=2&rank=2 [Accessed January 21, 2021].