Combination of mesenchymal stem cell-conditioned medium and botulinum toxin type A for treating human hypertrophic scars

Background: Both mesenchymal stem cell-conditioned medium (MSC CM) and Botox have demonstrated therapeutic effects for hypertrophic scar (HS). It is unclear whether a synergistic effect occurs when these treatments are used in combination. We aimed to investigate the therapeutic effects of MSC CM and Botox alone when compared with those of a combined regimen on HS. Methods: Fibroblasts from human HS were isolated and treated with Dulbecco's modified Eagle's medium (DMEM), MSC[sbnd]CM, or Botox alone or a combination of MSC[sbnd]CM and Botox. We also used an in vivo HS-buried null mice model to investigate the efficacy of combination treatment. Results: The results demonstrated that the combination of MSC CM and Botox downregulated both mRNA and protein levels of type I collagen, type III collagen, and alpha-smooth muscle actin (α-SMA) in HS fibroblasts. The combined regimen also suppressed fibroblast proliferative activity, increased apoptosis, and displayed significant inhibitory effects on the contractile ability of HS fibroblasts compared to MSC CM, Botox, or DMEM alone. Using an in vivo HS-buried null mice model, significant scar weight reduction, cell apoptosis, and less α-SMA expression were observed from the combined regimen of MSC CM and Botox compared to those from the other groups. The combined regimen also significantly improved arrangement and deposition of collagen fibers. Conclusions: This study demonstrates that a combination of MSC CM and Botox exhibited a significant therapeutic effect compared to monotherapy. Clinical translation of this therapy should be further considered.