TABLE 10.

Preclinical in vivo and clinical studies of hMSCs used as advanced therapy for hypertrophic scars in the last 5 years.

PRECLINICAL IN VIVO STUDIES
Type of advanced therapy	Cells		Type of hMSC treatment evaluated			Animals	Disease models		Follow-up	References
Cell therapy	hAT-MSCs		1-hAT-MSCs group: subcutaneous injection of 106 cells 2-Stromal vascular fraction (SVF) group subcutaneous injection of SVF containing 106 hAT-MSCs 3-Control group: subcutaneous injection of phosphate buffered saline			30 Athymic Nude-Foxn1nu (10 mice per group)	Human skin samples were grafted into mice for 7 weeks to develop hypertrophic scars		21 days	Domergue et al., 2016
	hBM-MSCs		1-hBM-MSCs group: addition to the wound of 106 cells/ml 2-hBM-MSCs + collagen I-tenascin-C (TNC) group: addition to the wound of 106 cells/ml + collagen I-tenascin-C (TNC) 3-hBM-MSCs + fibroblasts + hyaluronic acid (HA) group: addition to the wound of 106 cells/ml + fibroblasts + HA 4-hBM-MSCs + fibroblasts + collagen I-TNC + hyaluronic acid (HA) group: addition to the wound of 106 cells/ml + fibroblasts + collagen I-TNC + HA			– C57BL/6J wild-type and CXCR3 expression-abrogated mice	Wounds these mice presented a visible scar, a thickened epidermis, and a disorganized and hypercellular dermis		30 days	Yates et al., 2017
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	Allogenic hUCB-MSCs	Phase II Randomized Clinical Trial (Parallel Assignment- Triple Blind)	90 (0/90)	28.04 ± 3.39	A transdermal application of 106 cells for continuous 3 days (low-dose) or for continuous 6 days (high-dose) or placebo	No obvious side effects or adverse effects were reported	Caesarean Section Scars	Vancouver Scar Scale (VSS) score after 6 months was lower in the case of the high-dose group against low-dose and placebo groups (4.71, 5.18 and 6.43, respectively)	6 months and 36 months	Fan et al., 2018; Fan et al., 2020 NCT02772289 (Perinatal Tissue Mesenchyme Stem Cells in the Treatment for Caesarean Section Scars – Full Text View – ClinicalTrials.gov)1 NCT04034615 (Injection of Autologous Adipose-derived Stromal Vascular Fraction in the Finger of Systemic Sclerosis Patients – Full Text View – ClinicalTrials.gov)2

^aExpression of measures: mean ± standard deviation (range).

¹Perinatal Tissue Mesenchyme Stem Cells in the Treatment for Caesarean Section Scars – Full Text View – ClinicalTrials.gov Available at: https://clinicaltrials.gov/ct2/show/NCT02772289 [Accessed February 14, 2021].

²Injection 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].