Cysteinamide Enhances Fibroblast Survival and Wound Healing by Preventing Serum Deterioration in High-Glucose...

In patients with diabetes, persistent hyperglycemia causes chemical changes in serum components, increasing the incidence of various complications such as skin wounds. To better understand glucose-associated chemical stress on serum components, this study explores small-molecule nutrients to protect human dermal fibroblasts (HDFs) from glucose-rich, chemically deteriorated culture conditions.

Various cell culture media with different concentrations of glucose and various test compounds were subjected to heat treatment as a chemically accelerated model of serum deterioration. The heat-treated and non-heat-treated media were compared to each other in terms of the content of glycation products and their effects on cell viability and wound healing in vitro.

There was no difference in the content of glycation products or their effects on cell viability between the non-heat-treated low-glucose (LG, 5.5 mm) and high-glucose (HG, 50 mm) media that were not heat treated. However, the heat-treated HG media had a higher content of glycation products and decreased cell viability compared to the heat-treated LG media. Of the 20 free amino acids, 20 amidated amino acids and various antioxidants derived from cysteine (Cys) or ascorbic acid (AA) added to the media, followed by heat treatment, only cysteinamide (C-NH₂) enhanced the viability and wound healing of HDFs cultured in the heat-treated HG media. C-NH₂ reduced glycation of serum proteins while forming its own glycation products, suggesting a competitive interaction with glucose-derived reactions.

These findings provide proof-of-concept evidence that C-NH₂ can protect serum components and improve fibroblast-associated wound closure under chemically stressed, glucose-rich conditions. Further studies using physiologically relevant models are required to evaluate its biological and translational significance.