Copyright ©The Author(s) 2021.
World J Stem Cells. Jan 26, 2021; 13(1): 30-48
Published online Jan 26, 2021. doi: 10.4252/wjsc.v13.i1.30
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
Bleomycin-induced lung fibrosis mouse modelHuman ADSC administrationAmelioration of cuboidal alveolar epithelial cell hyperplasia, alveolar duct infiltration, septal thickening and tissue fibrosis. Suppression of epithelial cell apoptosis and reduction of TGF-β expressionLee et al[47], 2014
Aged mouse model of bleomycin-induced lung fibrosisSingle intravenous injection of allogeneic ADSCsAttenuation of lung and skin fibrosisRubio et al[48], 2018
Bleomycin-induced lung injury rat modelIntratracheal administration of autologous ADSCsPrevention of further aggravation of lung damage at day 15 after disease inductionUji et al[49], 2015
Bleomycin-induced lung fibrosis mouse modelAdministration of ADSCs from aged and young miceDecreased pulmonary fibrosis, oxidative stress, and markers of apoptosis only in animals receiving young ADSCs at day 21 after bleomycin instillationTashiro et al[50], 2015
Bleomycin-induced skin sclerosis model in nude miceLocal subcutaneous injections of human micro-fat enriched with SVFDecrease in the established dermal fibrosis and increase in local vascularizationSerratrice et al[51], 2014
Bleomycin-induced skin sclerosis model in nude miceHuman ADSC-assisted local subcutaneous lipotransferReduced TGF-β1 and type III collagen expressionChen et al[52], 2018
Bleomycin-induced skin fibrosis mouse modelSubcutaneous injection of autologous ADSCsAmelioration of dermal fibrosisChen et al[53], 2017
Bleomycin-induced scleroderma and Scl-cGVHD mouse modelsIntravenous administration of allogeneic ADSCsAttenuation of skin and lung fibrosisOkamura et al[54], 2020
Bleomycin-induced skin fibrosis mouse modelIntradermal injection of allogeneic ADSCsProvision of dendritic cell-derived signals improved survival and effectiveness of therapeutically delivered ADSCsChia et al[55], 2016
HOCl-induced mouse model of diffuse SScIntravenous injection of healthy murine and human ADSCsDecrease in skin and lung fibrotic and pro-inflammatory markersMaria et al[56], 2016
Table 2 Summary of fat grafting and adipose-derived stem cell-based treatments in systemic sclerosis
No. of patients
Follow-up period
Results (face)
1-Autologous fat grafting improved perioral aesthetic appearance and mouth openingHo-Asjoe et al[58], 1996
203 moAutologous fat grafting increased interincisal distance, oral perimeter and induced skin neovascularizationDel Papa et al[60], 2015
146 moAutologous fat grafting improved perioral skin sclerosis, facial pain, mouth opening and sicca syndromeSautereau et al[61], 2016
712 moAutologous fat grafting improved SSc-related microstomia and microcheiliaBlezien et al[62], 2017
163 moAutologous fat transfer significantly improved mouth opening capacityGheisari et al[63], 2018
1-Autologous fat grafting enriched with PRP improved skin trophicityDaumas et al[13], 2020
63 moThe combined use of autologous lipoaspirate and PRP improved buccal rhyme, skin elasticity, and vascularization of the perioral and malar areasVirzì et al[64], 2017
612 moLocal injection of autologous ADSCs in combination with a hyaluronic acid solution led to arrest of local disease progression, regression of dyschromia, better sensitivity, increase in skin softening and erythema reductionScuderi et al[23], 2013
1012 moBoth autologous fat grafting and ADSC-enriched hyaluronic acid gel improved mouth opening and interincisal distanceOnesti et al[65], 2016
626-53 moAutologous ADSC-enriched lipotransfer significantly improved mouth function, facial volumetric appearance and psychological outcomeAlmadori et al[3], 2019
Table 3 Summary of fat grafting and stromal vascular fraction-based treatments in systemic sclerosis
No. of patients
Follow-up period
Results (hands)
139.4 to 24.3 moAutologous fat implantation led to significant pain relief and decrease in the number, duration, and severity of Raynaud’s phenomenon cold attacksBank et al[66], 2014
912 wkAutologous fat grafting was effective in accelerating the healing process of DUs and led to a significant reduction in hand pain and need of pharmacological therapyBene et al[67], 2014
156 moAutologous SVF injections led to prompt disappearance of local ischemic pain, rapid DU healing and improvement in nailfold capillaroscopy abnormalitiesDel Papa et al[68], 2015
388 wkAutologous fat grafting induced DU healing, restoration of the capillary bed and a rapid resolution of local ischemic painDel Papa et al[14], 2019
126 moInjection of autologous SVF proved to be safe, well tolerated and beneficial in terms of pain, grasping capacity, finger edema, Raynaud’s phenomenon, DU outcome and quality of lifeGranel et al[69], 2015
1212 moThe effects recorded by Granel et al[69] proved to be long lasting, as they persisted 1 yr after SVF injectionGuillaume-Jugnot et al[70], 2016
1222-30 moThe effects recorded by Granel et al[69] were still very encouraging even at 22 and 30 mo after treatmentDaumas et al[72], 2017
1-Autologous SVF subcutaneous injections had beneficial effects on digital necrosis, ulceration, gangrene and impaired wound healingSong et al[73], 2017