Abstract
BackgroundHypertrophic scars (HSs) are formed via an aberrant response to the wound healing process. HSs can be cosmetic or can result in functional problems. Prolonged proliferation and remodeling phases disrupt wound healing, leading to excessive collagen production and HS formation. However, there are currently no satisfactory drugs to prevent HS formation. Mesenchymal stem cell (MSC) conditioned medium (CM) has therapeutic effects on wound healing and preventing HS formation. Bone marrow concentrate (BMC) contains various growth factors and cytokines that are crucial for regeneration and has been applied in the clinical setting. In this study, we evaluated the effects of BMC-induced MSC CM on HS formation in a rabbit ear model.MethodsWe established a rabbit ear wound model by generating full-thickness wounds in the ears of rabbits (n = 12) and treated wounds with MSC CM, BMC CM, or BMC-induced MSC CM. Dermal fibroblasts from human hypertrophic scar were stimulated with transforming growth factor beta 1 (TGF-β1) for 24 h and cultured in each culture medium for 72 h. We measured the hypertrophic scar (HS) formation during the skin regeneration by measuring the expression of several remodeling molecules and the effect of these conditioned media on active human HS fibroblasts.ResultsOur results showed that BMC-induced MSC CM had greater antifibrotic effects than MSC CM and BMC CM significantly attenuated HS formation in rabbits. BMC-induced MSC CM accelerated wound re-epithelization by increasing cell proliferation. Additionally, BMC-induced MSC CM also inhibited fibrosis by decreasing profibrotic gene and protein expression, promoting extracellular matrix turnover, inhibiting fibroblast contraction, and reversing myofibroblast activation.ConclusionsBMC-induced MSC CM modulated the proliferation and remodeling phases of wound healing, representing a potential wound healing agent and approach for preventing HS formation.
Highlights
Hypertrophic scars (HSs) are a common complication of burns and other soft tissue injuries
Rabbit ears treated with Bone marrow concentrate (BMC)-induced Mesenchymal stem cell (MSC) conditioned medium (CM) healed significantly faster than rabbit ears in the other groups, and complete closure occurred on day 28 after the operation
BMC-induced MSC CM reduced the contractile ability of HS in collagen gels To investigate the effects of BMC-induced MSC CM on the contractile ability and functions of HSs, we examined the properties of human HS-derived fibroblasts in three-dimensional (3D) fibroblast function assays
Summary
Hypertrophic scars (HSs) are a common complication of burns and other soft tissue injuries. Several treatments for HSs, including surgical excision, intralesional corticosteroid injection, compression, laser treatment, and interferon injection, have been developed to date [1]. These treatments are not effective for preventing excessive scar tissue formation and regenerating healthy tissue. BMC is an autologous bone marrow-derived product that provides a heterogeneous mixture of cells and a variety of bioactive growth factors and cytokines associated with wound healing [3]. Mesenchymal stem cell (MSC) conditioned medium (CM) has therapeutic effects on wound healing and preventing HS formation. Bone marrow concentrate (BMC) contains various growth factors and cytokines that are crucial for regeneration and has been applied in the clinical setting. We evaluated the effects of BMC-induced MSC CM on HS formation in a rabbit ear model
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