Bone marrow concentrate-induced mesenchymal stem cell conditioned medium facilitates wound healing and prevents hypertrophic scar formation in a rabbit ear model

Abstract

Background Hypertrophic 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. Methods We 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. Results Our 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. Conclusions BMC-induced MSC CM modulated the proliferation and remodeling phases of wound healing, representing a potential wound healing agent and approach for preventing HS formation. Electronic supplementary material The online version of this article (10.1186/s13287-019-1383-x) contains supplementary material, which is available to authorized users.

The Potential of a Hair Follicle Mesenchymal Stem Cell-Conditioned Medium for Wound Healing and Hair Follicle Regeneration

“…Previous study found that caffeic acid produced low cytotoxicity of keratinocytes that can induce cell proliferation and differentiation [22]. Furthermore, another study confirmed that cell proliferation could also be elevated by means of CM from culture MSC [13]. In this study, we found treatment with MSC-CM exhibited the highest cell proliferation in both HFMSC and HaCaT keratinocyte during wound healing.…”

“…The cytokines and growth factors play a crucial role in activating and stimulating fibroblast proliferation during the wound healing process [11]. Previous studies have reported positive results of wound healing and skin repair by utilizing CM from cultured MSCs (MSC-CM) derived from different sources such as bone marrow mesenchymal stem cell (BM-MSC) [9,12,13], adipose stem cell [14][15][16], Wharton's jelly-derived MSC [17], and human umbilical MSC [1]. Furthermore, numerous studies have proven that several kinds of drugs can be potentially used to promote cell growth and proliferation that is beneficial for wound healing and hair regeneration including UK5099 [18], sodium L-lactate (SLL) [19], lactate dehydrogenase-A (LDHA) [18], caffeine [20,21], and caffeic acid (CFA) [22].…”

Mesenchymal stem cell therapy in hypertrophic and keloid scars

“…Six studies used bone marrow MSCs: two of murine origin (Hu et al 2019(Hu et al , 2020, two of human origin , one of rabbit origin , and one study included both human and rabbit origin MSCs . Five of the studies that employed bone marrow MSCs harvested cells by needle aspiration from either the tibia, femur or posterior iliac crest (Hu et al 2019(Hu et al , 2020. One study, by Yates et al used bone marrow MSCs derived from an immortalised cell line.…”

Combination of Lyophilized Adipose-Derived Stem Cells Concentrated Conditioned Medium and Polysaccharide Hydrogel in the Inhibition of Hypertrophic Scarring

“…With ascending evidence in the eld of the validity of stem cell supernatant in remission of scarring [28,29], there is a good rationale for pursuing the development of ADSCC-CM as new potential therapeutic agents. Notably, α-SMA and collagen deposition related to the activity of the TGF-β/Smad2 signalling pathway participates in the transition of broblasts/myo broblasts [30].…”