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 α-smooth muscle actin (α-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 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. Conclusions Altogether, 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.

Human Mesenchymal Stromal Cell-Derived Exosomes Promote In Vitro Wound Healing by Modulating the Biological Properties of Skin Keratinocytes and Fibroblasts and Stimulating Angiogenesis

“…In recent years, the therapeutic application of bone marrow-derived mesenchymal stromal/stem cells (MSCs) shifted from cellular transplantation to acellular therapy, in light of a novel mechanism of action, based on the favorable effects of factors secreted by these cells. Previous work, including our own, supports the use of MSC conditioned medium (CM) for skin wound healing, on account of its stimulative properties on several key biological processes such as proliferation, migration, and angiogenesis [4][5][6][7][8][9]. Besides growth factors and cytokines, the CM (the secretome) also includes the ubiquitous large family of extracellular vesicles (EVs) comprising exosomes, microvesicles (microparticles), and apoptotic bodies.…”

Evaluation of the Effects of Human Dental Pulp Stem Cells on the Biological Phenotype of Hypertrophic Keloid Fibroblasts

“…Furthermore, stem cells have been shown to improve tissue repair by secreting interleukins such as interleukin 6, interleukin 8, interleukin 10 and other proteins that are suitable for inducing tissue regeneration [ 21 , 22 ]. Recent studies have shown that adipose-derived stem cells are able to inhibit mRNA expression levels of COL1A1, transforming growth factor β1, connective tissue growth factor and alpha actin 2 (ACTA2) in renal fibrosis tissues, thereby playing a therapeutic role in renal fibrosis [ 23 ]. Whether or not dental pulp stem cells can play a role in the repair of skin scars by inhibiting the proliferation and migration of keloid fibroblasts through the secretion of cytokines has not been clearly reported thus far.…”

Effects of Mesenchymal Stem Cell-Derived Exosomes on Autoimmune Diseases

“…In the experimental model of ischemia, the retention time of MSC-EXOs with an injectable hydrogel was prolonged, which enhanced the therapeutic effect of exosomes ( 127 ). In the experiment of preventing hyperplastic scar in rabbit ear model, adipose-derived stem cell conditioned Medium (ADSC-CM) was combined with polysaccharide hydrogel to prolong the therapeutic effect of cytokines ( 128 ). Third, in order to ensure the safety of patients treated with MSC-EXOs, the route and dose of exosomes must be explored.…”