Intralesional injection of adipose-derived stem cells reduces hypertrophic scarring in a rabbit ear model

Abstract BackgroundMesenchymal stem cell-based acellular therapies have been widely exploited in managing hypertrophic scar. However, low maintenance dose and transitory therapeutic effects during topical medication remain a thorny issue. Herein, this study aimed to optimize the curative effect of adipose-derived stem cells conditioned medium (ADSC-CM) in the prevention of hypertrophic scarring. MethodsIn the present study, ADSC-CM was concentrated via the freeze-drying procedure. The efficacy of different dose groups (CM, CM5, CM10) was conducted on the proliferation, apoptosis, and α-smooth muscle actin (α-SMA) expression of human keloid fibroblasts (HKFs) in vitro. Incorporation of adipose-derived stem cells concentrated conditioned medium (ADSCC-CM) into polysaccharide hydrogel was investigated in rabbit ear, in vivo. Haematoxylin-eosin (H&E) and Masson's trichrome staining were performed for the evaluation of scar hyperplasia. ResultsWe noted that ADSCC-CM could downregulate the α-SMA expression of HKFs in a dose-dependent manner. In the rabbit ear model, the scar hyperplasia in the medium-dose group (CM5) and high-dose group (CM10) was inhibited with reduced scar elevation index (SEI) under 4 months of observation. It is noteworthy that the union of CM5 and polysaccharide hydrogel (CM5+H) yielded the best preventive effect on scar hyperplasia. Briefly, melanin, height, vascularity and pliability in the CM5+H group were better than those of the control group. Collagen was evenly distributed, and skin appendages could be regenerated.ConclusionsAltogether, ADSCC-CM can downregulate the expression of α-SMA due to its anti-fibrosis effect, and promote the rearrangement of collagen fibres, which is integral to scar precaution. The in situ cross bonding of ADSCC-CM and polysaccharide hydrogel could remarkably enhance the therapeutic outcomes in inhibiting scar proliferation. Hence, the alliance of ADSCC-CM and hydrogel may become a potential alternative in hypertrophic scar prophylaxis.

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Hepatocyte Growth Factor Secreted from Human Adipose-Derived Stem Cells Inhibits Fibrosis in Hypertrophic Scar Fibroblasts

Current Molecular Medicine ◽

10.2174/1566524020666200106095745 ◽

2020 ◽

Vol 20 (7) ◽

pp. 558-571 ◽

Cited By ~ 6

Author(s):

Ji Ma ◽

Xin Yan ◽

Yue Lin ◽

Qian Tan

Keyword(s):

Stem Cells ◽

Growth Factor ◽

Hepatocyte Growth Factor ◽

Hypertrophic Scar ◽

Collagen Type ◽

Smooth Muscle Actin ◽

Adipose Derived Stem Cells ◽

Collagen Production ◽

Rabbit Ear ◽

Hepatocyte Growth

Aims: To study the effect of Adipose-derived stem cells (ADSCs) on fibrosis of hypertrophic scar-derived fibroblasts (HSFs) and its concrete mechanism. Background: ADSCs have been reported to reduce collagen production and fibroblast proliferation in co-culture experiments. Conditioned medium from adipose-derived stem cells (ADSCs-CM) has successfully inhibited fibrosis by decreasing the expression of collagen type І (Col1) and α-smooth muscle actin (α-SMA) in rabbit ear scar models. Hepatocyte growth factor (HGF), the primary growth factor in ADSCs-CM, has been shown to reverse fibrosis in various fibrotic diseases. Background: ADSCs have been reported to reduce collagen production and fibroblast proliferation in co-culture experiments. Conditioned medium from adipose-derived stem cells (ADSCs-CM) has successfully inhibited fibrosis by decreasing the expression of collagen type І (Col1) and α-smooth muscle actin (α-SMA) in rabbit ear scar models. Hepatocyte growth factor (HGF), the primary growth factor in ADSCs-CM, has been shown to reverse fibrosis in various fibrotic diseases. Objective: To test the hypothesis that ADSCs inhibit fibrosis of HSFs through the secretion of HGF. Methods: HSFs were treated with DMEM containing 0%, 10%, 50% and 100% concentration of ADSCs-CM. The effect of ADSCs-CM on the viability was determined by cell viability assay, and the collagen production in HSFs was examined by Sirius red staining. Expression and secretion of fibrosis and degradation proteins were detected separately. After measuring the concentration of HGF in ADSCs-CM, the same number of HSFs were treated with 50% ADSCs-CM or HGF. HGF activity in ADSCs-CM was neutralized with a goat anti-human HGF antibody. Results: The results demonstrated that ADSCs-CM dose-dependently decreased cell viability, expression of fibrosis molecules, and tissue inhibitor of metalloproteinases-1 (TIMP-1), and significantly increased matrix metalloproteinase-1 (MMP-1) expression in HSFs. Collagen production and the ratio of collagen type І and type III (Col1/Col3) were also suppressed by ADSCs-CM in a dose-dependent manner. When HSFs were cultured with either 50% ADSCs-CM or HGF (1 ng/ml), a similar trend was observed in gene expression and protein secretion. Adding an HGF antibody to both groups returned protein expression and secretion to basal levels but did not significantly affect the fibrosis factors in the control group. Conclusion: Our findings revealed that adipose-derived stem cell-secreted HGF effectively inhibits fibrosis-related factors and regulates extracellular matrix (ECM) remodeling in hypertrophic scar fibroblasts.

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Differentiation of adipose-derived stem cells into ear auricle cartilage in rabbits

The Journal of Laryngology & Otology ◽

10.1017/s0022215112001065 ◽

2012 ◽

Vol 126 (8) ◽

pp. 770-774 ◽

Cited By ~ 18

Author(s):

H Bahrani ◽

M Razmkhah ◽

M J Ashraf ◽

N Tanideh ◽

N Chenari ◽

...

Keyword(s):

Stem Cells ◽

Histopathological Examination ◽

Cartilage Tissue ◽

Control Group ◽

Adipose Derived Stem Cells ◽

Rabbit Ear ◽

Ear Auricle ◽

Cartilage Injuries ◽

Surgically Induced

AbstractBackground:Adipose-derived stem cells have been reported as a novel candidate for the repair of cartilage injuries in vivo.Methods:In order to assess their differentiation ability, adipose-derived stem cells isolated from rabbit fat tissue were injected into the midportion of a surgically created rabbit ear auricle cartilage defect. After several months, the auricles were resected, histopathologically assessed and compared with a control group.Results:Histopathological examination of auricles removed three, four and five months after injection showed islands of new cartilage formation at the site of the surgically induced defect. Six months after injection, we observed well-formed, mature cartilaginous plates that completely filled the defect in the native cartilage. In the control group, there was no significant growth of new cartilage.Conclusion:The results of this study suggest the great potential of adipose-derived stem cells to repair damaged cartilage tissue in vivo.

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