Dataset Information

Combination of lyophilized adipose-derived stem cell concentrated conditioned medium and polysaccharide hydrogel in the inhibition of hypertrophic scarring.

ABSTRACT:

Background

Mesenchymal stem cell-based acellular therapies have been widely exploited in managing hypertrophic scars. 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 cell conditioned medium (ADSC-CM) in the prevention of hypertrophic scarring.

Methods

In 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 ?-smooth muscle actin (?-SMA) expression of human keloid fibroblasts (HKFs) in vitro. Incorporation of adipose-derived stem cell 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.

Results

We noted that ADSCC-CM could downregulate the ?-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.

Conclusions

Altogether, ADSCC-CM can downregulate the expression of ?-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.

SUBMITTER: Zhang C

PROVIDER: S-EPMC7792059 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Combination of lyophilized adipose-derived stem cell concentrated conditioned medium and polysaccharide hydrogel in the inhibition of hypertrophic scarring.

Zhang Chaoyu C Wang Ting T Zhang Li L Chen Penghong P Tang Shijie S Chen Aizhen A Li Ming M Peng Guohao G Gao Hangqi H Weng Haiyan H Zhang Haoruo H Li Shirong S Chen Jinghua J Chen Liangwan L Chen Xiaosong X

Stem cell research & therapy 20210107 1

<h4>Background</h4>Mesenchymal stem cell-based acellular therapies have been widely exploited in managing hypertrophic scars. 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 cell conditioned medium (ADSC-CM) in the prevention of hypertrophic scarring.<h4>Methods</h4>In the present study, ADSC-CM was concentrated via the freeze-drying procedure. The ef ...[more]

PMID: 33413617

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Project description:Lyophilization is the process of drying and improving the stability of various pharmaceutical preparations. In this work we evaluated the properties of 11 hydrophilic gels calcium dobesilate with liposomes based on soybean lecithin, subjected to the freeze-drying procedure. Liposomes were produced by using method thin lipid film. Lyophilization was carried out under conditions of temperature equal (-30 °C) and pressure 0.37 mbar. We evaluated the preparations with dynamic light scattering (DLS) method, optical microscopy and Fourier-transform infrared spectroscopy (FTIR). In this work we presented the average results for the particle diameter in the sample and PDI (polydispersity index) value for the samples that produced the results. When testing using the DLS method on a Malvern Zetaseizer, results for 7 samples were not obtained. Two of next four samples were characterized by an increased size of the liposome particle resulting from a lower concentration of ethanol compared to the rest of them. Three samples under the microscope did not show any differences. It was possible only to see single crystals probably of undissolved calcium dobesilate. Some clusters were observed in the 4 samples, and when they appeared they were very small. The aggregates and irregular liposomes present in the rest of the samples may have been formed due to the destabilizing activity of ethanol towards lipid membranes. In the FTIR spectrum for MC, the peak was observed at the wavenumber of ca. 2900 cm-1 and of about 1050 cm-1. In case of pure calcium dobesilate we observed low pick at the wavenumber of about 3400 cm-1. The spectrum has a low peak at the wavenumber of 1450 cm-1 and intense peaks ranging from approx. 1000 cm-1 to approx. 1200 cm-1. Decay of the lecithin peak in formulations with liposomes at 1725 cm-1 wavelength may indicate the occurrence of the hydrolysis reaction in the system. Probably there was a hydrolysis of the ester bond connecting the rest of the phosphoric acid and the choline with the glycerol residue.

Project description:UnlabelledAdipose-derived stem cells (ASCs) mainly exert their function by secreting materials that are collectively termed the secretome. Despite recent attention to the secretome as an alternative to stem cell therapy, the culture conditions for generating optimal secretome contents have not been determined. Therefore, we investigated the role of hypoxic-conditioned media (HCM) from ASCs. Normoxic-conditioned media (NCM) and HCM were obtained after culturing ASCs in 20% O2 or 1% O2 for 24 hours, respectively. Subsequently, partially hepatectomized mice were infused with saline, control medium, NCM, or HCM, and then sera and liver specimens were obtained for analyses. Hypoxia (1% O2) significantly increased mRNA expression of mediators from ASCs, including interleukin-6 (IL-6), tumor necrosis factor ? (TNF-?), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF). HCM infusion significantly increased the number of Ki67-positive cells in the liver (p < .05). HCM infusion significantly increased phospho-signal transducer and activator of transcription 3 (STAT3) and decreased suppressor of cytokine signaling 3 (SOCS3) expression in the liver (p < .05). To determine the role of IL-6 in liver regeneration, we then performed IL-6 RNA interference study. Conditioned media (CM) obtained from ASCs, which were transfected with either siIL-6 or siControl, were administered to partially hepatectomized mice. The siIL-6 CM groups exhibited lower liver proliferation (Ki67-positive cells) and markers of regeneration (protein expression of proliferating cell nuclear antigen, p-STAT3, HGF, and VEGF and liver weights) than the siControl CM groups (p < .05). Taken together, hypoxic preconditioning of ASCs increased expression of mediators promoting anti-inflammatory and regenerative responses. The liver regenerative effects of HCM appear to be mediated by persistent and uninhibited expression of STAT3 in the liver, which results from decreased expression of SOCS3.SignificanceIn this study, it was found that treatment with the medium from hypoxic-preconditioned adipose-derived stem cells (ASCs) increased the viability of hepatotoxic hepatocytes and enhance liver regeneration in partially hepatectomized mice. In addition, the researchers first revealed that the hepatoprotective effects of hypoxic-conditioned media are mediated by persistent and uninhibited expression of signal transducer and activator of transcription 3 in the liver, which result from a decreased expression of suppressor of cytokine signaling 3. Therefore, the hypoxic preconditioning of ASCs is expected to play a crucial role in regenerative medicine by optimizing the production of a highly effective secretome from ASCs.

Dataset Information

Combination of lyophilized adipose-derived stem cell concentrated conditioned medium and polysaccharide hydrogel in the inhibition of hypertrophic scarring.

Background

Methods

Results

Conclusions

Publications

Combination of lyophilized adipose-derived stem cell concentrated conditioned medium and polysaccharide hydrogel in the inhibition of hypertrophic scarring.

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