Molecular and Histological Evidence Detailing Clinically Observed Skin Improvement Following Cryolipolysis

BACKGROUND: In addition to body contouring, there is anecdotal and clinical evidence of reduced laxity caused by skin tightening after cryolipolysis. However, it has not been established how cryolipolysis triggers dermal changes. OBJECTIVES: The aim of this study was to investigate the fundamental mechanisms behind clinically observed dermal changes by molecular and immunohistochemistry (IHC) analytical methods. METHODS: This feasibility study involved 7 subjects who received cryolipolysis treatment. Tissue samples were harvested from 3 days to 5 weeks after treatment. RNA-sequencing examined differential gene expression of major collagens. RNA in situ hybridization (RNA-ISH) investigated the distribution of 1 of the gene markers for collagen type I (COL1A1). IHC for procollagen type I, heat shock protein 47 (HSP47), transforming growth factor β (TGF-β), and tropoelastin was performed and quantified. RESULTS: Gene expression analysis highlighted a gradual upregulation of collagen mRNA genes. RNA-ISH confirmed upregulation of COL1A1 mRNA and showed a homogeneous distribution through the dermis. IHC showed increases in protein expression. Quantification revealed a 3.62-fold increase of procollagen type I (P < 0.0071), a 2.91-fold increase of TGF-β (P < 0.041), a 1.54-fold increase of HSP47 (P < 0.007), and a 1.57-fold increase of tropoelastin (P < 0.39) compared with untreated areas. CONCLUSIONS: This study revealed significant induction of molecular and protein markers of type I collagen, which supports neocollagenesis and may play an essential role in clinically relevant skin improvement. A dermal remodeling process driven by increased TGF-β and higher expression of HSP47 was observed. Overall, these data provide the first evidence of dermal remodeling and clarify the mechanism by which cryolipolysis may induce skin improvement. LEVEL OF EVIDENCE: 4: [Image: see text]