Molecular and Histological Evidence Detailing Clinically Observed Skin Improvement Following Cryolipolysis.

BACKGROUND In addition to body contouring, there is anecdotal and supportive clinical evidence of reduced laxity and skin tightening after cryolipolysis. 10,11. OBJECTIVES The nature by which cryolipolysis triggers dermal changes has not been established. This study investigated fundamental mechanisms behind clinically observed dermal changes using molecular and immunohistochemistry methods. METHODS This feasibility study involved n=7 subjects that 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 one of the gene markers for collagen Type I (COL1A1). Immunohistochemistry for Procollagen Type I, heat shock protein 47 (HSP47), transforming growth factor beta (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 homogenous distribution through the dermis. Immunohistochemistry showed increases in protein expression. Quantification revealed 3.62-fold increase of Procollagen Type I (p<0.0071) and 2.91-fold increase of TGF-β (p<0.041); 1.54-fold increase of HSP47 (p<0.007); and 1.57-fold increase of Tropoelastin (p<0.39) compared to 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.