Abstract
IntroductionRedundant collagen deposition at sites of healing dermal wounds results in hypertrophic scars. Adipose-derived stem cells (ADSCs) exhibit promise in a variety of anti-fibrosis applications by attenuating collagen deposition. The objective of this study was to explore the influence of an intralesional injection of ADSCs on hypertrophic scar formation by using an established rabbit ear model.MethodsTwelve New Zealand albino rabbits were equally divided into three groups, and six identical punch defects were made on each ear. On postoperative day 14 when all wounds were completely re-epithelialized, the first group received an intralesional injection of ADSCs on their right ears and Dulbecco’s modified Eagle’s medium (DMEM) on their left ears as an internal control. Rabbits in the second group were injected with conditioned medium of the ADSCs (ADSCs-CM) on their right ears and DMEM on their left ears as an internal control. Right ears of the third group remained untreated, and left ears received DMEM. We quantified scar hypertrophy by measuring the scar elevation index (SEI) on postoperative days 14, 21, 28, and 35 with ultrasonography. Wounds were harvested 35 days later for histomorphometric and gene expression analysis.ResultsIntralesional injections of ADSCs or ADSCs-CM both led to scars with a far more normal appearance and significantly decreased SEI (44.04 % and 32.48 %, respectively, both P <0.01) in the rabbit ears compared with their internal controls. Furthermore, we confirmed that collagen was organized more regularly and that there was a decreased expression of alpha-smooth muscle actin (α-SMA) and collagen type Ι in the ADSC- and ADSCs-CM-injected scars according to histomorphometric and real-time quantitative polymerase chain reaction analysis. There was no difference between DMEM-injected and untreated scars.ConclusionsAn intralesional injection of ADSCs reduces the formation of rabbit ear hypertrophic scars by decreasing the α-SMA and collagen type Ι gene expression and ameliorating collagen deposition and this may result in an effective and innovative anti-scarring therapy.
Highlights
Redundant collagen deposition at sites of healing dermal wounds results in hypertrophic scars
Identification of adipose-derived stem cell (ADSC) ADSCs exhibited fibroblast morphology and expanded when cultured in regular medium in vitro. They were confirmed positive for CD73, CD90, and CD105 and negative for CD34, CD45, CD14, and HLA-DR expression according to flow cytometry analysis of stem cell-related surface markers (Fig. 2a)
They can be successfully trans-differentiated into adipocytes and osteocytes, and this was confirmed by using oil red O staining and alizarin red S (Fig. 2b). Both ADSC and ADSCs-CM treatments reduce scar hypertrophy Gross examination On postoperative day 14, all wounds were totally reepithelialized on gross examination
Summary
Redundant collagen deposition at sites of healing dermal wounds results in hypertrophic scars. After injury in dermal tissue, hypertrophic scars can occur because of abnormal extracellular matrix deposition and remodeling, especially with collagen [1]. This scar tissue is usually raised and inflexible with itching, pain, and redness as a result of an overabundant wound matrix and might give rise to significant. TGF-β1 inhibits matrix metalloproteinase (MMP) expression resulting in the accumulation of collagen fibers within the wound sites [11,12,13]. Myofibroblast differentiation is another intensifier of fibrosis during wound healing. It is very important to ensure the formation of an adequate microvascular network and development into a permanent vascular network during the healing process; otherwise, wound closure will be impaired and hypertrophic scars will occur [16]
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