TABLE 9.
Preclinical in vivo and clinical studies of hMSCs used as advanced therapy for scleroderma 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 | hBM-MSCs and hAT-MSCs | 1-hBM-MSCs group: intravenous infusion of 2.5 × 105 cells 2-hAT-MSCs group: intravenous infusion of 2.5 × 105 cells 3-Control group: no-treatment of systemic sclerosis induced mice | Daily intradermal injections of hypochlorite (HOCl) to induce systemic sclerosis (SSc) for 21 days | 21 days | Maria et al., 2016 | |||||
| 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 | Autologous hAT-MSCs | Phase I Clinical Trial (Single Group Assignment- Open Label) | 12 (0/12) 11 patients with skin fibrosis (sclerodactyly) | 54.5 ± 10.3 (34.0–68.0) | 3.76 ± 1.85 (1.19–7.07)x106 cells were subcutaneously injected into each lateral side of digits | No serious adverse events occurred during follow-up. | Systemic sclerosis (SSc) | After 12 months a significant improvement of 46.8% for the Scleroderma Health Assessment Questionnaire, of 51.3% for the Cochin Hand Function Scale score and of 63.2% for the Raynaud’s condition score was observed | 6 and 12 months | Granel et al., 2015; Guillaume-Jugnot et al., 2015 NCT01813279 (Assessment of the Subcutaneous Reinjection of Human Autologous Adipose-derived Stromal Vascular Fraction (Celution® System) in the Hands of Patients Suffering From Systemic Sclerosis – Full Text View – ClinicalTrials.gov)3 |
| Allogeneic hUCB-MSCs | Case report | 2 (0/2) | 29.0 (28.0–30.0) | 2 × 106 cells/kg, infused intravenously – 2 treatments | None | Systemic sclerosis (SSc) | After one year of treatment, European Scleroderma Study Group activity index was reduced from 9.5 to 3.5 and 1.5, respectively | 14 months (12–16) | Wehbe et al., 2016 | |
| Allogeneic hUCB-MSCs | Phase I/II Clinical Trial (Single Group Assignment- Open Label) | 14 (3/11) | 37.4 ± 14.2 (19.0–67.0) | Three repeated plasmapheresis treatments on days 1, 3 and 5. On day 8, single hUCB-MSC infusion was injected (106 cells/kg) | Adverse events noted were upper respiratory tract infections reported by five patients and diarrhea reported by one patient during follow-up visits | Systemic sclerosis (SSc) | After 12 months of treatment, the mean Modified Rodnan skin score improved from 20.1 ± 3.1 to 13.8 ± 10.2 | 15.6 ± 4.3 months (7–21) | Zhang et al., 2017 NCT00962923 (Allogeneic Mesenchymal Stem Cells Transplantation for Systemic Sclerosis (SSc) – Full Text View – ClinicalTrials.gov)2 | |
| Autologous hAT-MSCs | Case report | 1 (0/1) | 62.0 | Subcutaneous injection of 2.72 × 106 cells | None | Systemic sclerosis (SSc) | No need to further amputation was demonstrated. | 3 weeks | Song et al., 2017 | |
| Autologous hAT-MSCs | Case report | 6 (2/4) | 9.3 ± 7.1 (3.0–20.0) | Co-injection of PRP and hAT-MSCs | None | Cutaneous systemic sclerosis (dcSSc) | Skin elasticity was increased (16.64% for the lip and the 17.80% for the cheek) | 3 months | Virzì et al., 2017 | |
| Allogeneic hBM-MSCs | Phase I/II Randomized Clinical Trial (Parallel Assignment- Quadruple Blind) | 10 | – | Intramuscular injections with 50 × 106 cells | – | Systemic sclerosis (SSc) – Digital ulcers (DUs) | – | 12 months | (Van Rhijn-Brouwer et al., 2018) NCT03211793 | |
| Autologous hAT-MSCs | Clinical Trial (Single Group Assignment- Open Label) | 7 | Older than 18 | Subcutaneous injection of hAT-MSCs | – | Systemic sclerosis (SSc) – Digital ulcers (DUs) | – | 12 weeks | NCT02975960 (ADMSCs for the Treatment of Systemic Sclerosis – Full Text View – ClinicalTrials.gov)1 | |
| Allogeneic hUCB-MSCs | Phase I/II Randomized Clinical Trial (Parallel Assignment- Quadruple-Blind) | 18 | Older than 18 | One or two infusions of 106 cells/kg at Month 0 and (in the case of two infusions) Month 3 | – | Systemic scleroderma | – | 12 months | NCT04356287 (Treatment With Human Umbilical Cord-derived Mesenchymal Stromal Cells in Systemic Sclerosis – Full Text View – ClinicalTrials.gov)5 | |
| Autologous hAT-MSCs | Early Phase I Clinical Trial (Single Group Assignment- Open Label) | 20 but only 18 completed the study (3/15) | 47 (42–57) | Subcutaneous injection of 3.61 (± 4.34) x106 hAT-MSCs | Three patients reported transient pallor in fingers which was resolved within 10 min after resting and warming | Systemic sclerosis (SSc) – Digital ulcers (DUs) | Raynaud’s Condition Scale presented slight improvement, but with no significance (from 5 to 6) | 24 weeks | Park Y. et al., 2020 NCT03060551 (Injection of Autologous Adipose-derived Stromal Vascular Fraction in the Finger of Systemic Sclerosis Patients – Full Text View – ClinicalTrials.gov)4 | |
aExpression of measures: mean ± standard deviation (range).
1ADMSCs for the Treatment of Systemic Sclerosis – Full Text View – ClinicalTrials.gov Available at: https://www.clinicaltrials.gov/ct2/show/NCT02975960?term=mesenchymal+stem+cells&recrs=abdefgh&cond=Scleroderma&strd_s=01%2F01%2F2015&strd_e=12%2F31%2F2020&draw=2&rank=1 [Accessed January 21, 2021].
2Allogeneic Mesenchymal Stem Cells Transplantation for Systemic Sclerosis (SSc) – Full Text View – ClinicalTrials.gov Available at: https://clinicaltrials.gov/ct2/show/NCT00962923 [Accessed February 14, 2021].
3Assessment of the Subcutaneous Reinjection of Human Autologous Adipose-derived Stromal Vascular Fraction (Celution§System) in the Hands of Patients Suffering From Systemic Sclerosis – Full Text View – ClinicalTrials.gov Available at: https://clinicaltrials.gov/ct2/show/NCT01813279 [Accessed February 14, 2021].
4Injection of Autologous Adipose-derived Stromal Vascular Fraction in the Finger of Systemic Sclerosis Patients – Full Text View – ClinicalTrials.gov Available at: https://clinicaltrials.gov/ct2/show/NCT03060551 [Accessed February 14, 2021].
5Treatment With Human Umbilical Cord-derived Mesenchymal Stromal Cells in Systemic Sclerosis – Full Text View – ClinicalTrials.gov Available at: https://www.clinicaltrials.gov/ct2/show/NCT04356287?term=mesenchymal+stem+cells&recrs=abdefgh&cond=Scleroderma&strd_s=01%2F01%2F2015&strd_e=12%2F31%2F2020&draw=2&rank=2 [Accessed January 21, 2021].