Adipose-derived stem cells: Pathophysiologic implications vs therapeutic potential in systemic sclerosis

Table 1 Summary of the main therapeutic effects of fat grafting and stromal vascular fraction/adipose-derived stem cells in preclinical models of systemic sclerosis-like pulmonary and skin fibrosis

Animal model	Treatment	Results	Ref.
Bleomycin-induced lung fibrosis mouse model	Human ADSC administration	Amelioration of cuboidal alveolar epithelial cell hyperplasia, alveolar duct infiltration, septal thickening and tissue fibrosis. Suppression of epithelial cell apoptosis and reduction of TGF-β expression	Lee et al[47], 2014
Aged mouse model of bleomycin-induced lung fibrosis	Single intravenous injection of allogeneic ADSCs	Attenuation of lung and skin fibrosis	Rubio et al[48], 2018
Bleomycin-induced lung injury rat model	Intratracheal administration of autologous ADSCs	Prevention of further aggravation of lung damage at day 15 after disease induction	Uji et al[49], 2015
Bleomycin-induced lung fibrosis mouse model	Administration of ADSCs from aged and young mice	Decreased pulmonary fibrosis, oxidative stress, and markers of apoptosis only in animals receiving young ADSCs at day 21 after bleomycin instillation	Tashiro et al[50], 2015
Bleomycin-induced skin sclerosis model in nude mice	Local subcutaneous injections of human micro-fat enriched with SVF	Decrease in the established dermal fibrosis and increase in local vascularization	Serratrice et al[51], 2014
Bleomycin-induced skin sclerosis model in nude mice	Human ADSC-assisted local subcutaneous lipotransfer	Reduced TGF-β1 and type III collagen expression	Chen et al[52], 2018
Bleomycin-induced skin fibrosis mouse model	Subcutaneous injection of autologous ADSCs	Amelioration of dermal fibrosis	Chen et al[53], 2017
Bleomycin-induced scleroderma and Scl-cGVHD mouse models	Intravenous administration of allogeneic ADSCs	Attenuation of skin and lung fibrosis	Okamura et al[54], 2020
Bleomycin-induced skin fibrosis mouse model	Intradermal injection of allogeneic ADSCs	Provision of dendritic cell-derived signals improved survival and effectiveness of therapeutically delivered ADSCs	Chia et al[55], 2016
HOCl-induced mouse model of diffuse SSc	Intravenous injection of healthy murine and human ADSCs	Decrease in skin and lung fibrotic and pro-inflammatory markers	Maria et al[56], 2016

SVF: Stromal vascular fraction; ADSCs: Adipose-derived stem cells; SSc: Systemic sclerosis; TGF-β: Transforming growth factor-β; Scl-cGVHD: Sclerodermatous chronic graft-versus-host disease; HOCl: Hypochlorous acid.