There is a need in plastic surgery to prepare autologous adipocytes that can be transplanted in patients to reconstruct soft tissue defects caused by
tumor resection, including
breast cancer, and by
trauma and other diseases. Direct conversion of somatic cells into adipocytes may allow sufficient functional adipocytes to be obtained for use in regeneration
therapy.
Chemical libraries of 10,800 molecules were screened for the ability to induce
lipid accumulation in human dermal fibroblasts (HDFs) in culture. Chemical compound-mediated directly converted adipocytes (CCCAs) were characterized by
lipid staining, immunostaining, and qRT-PCR, and were also tested for
adipokine secretion and
glucose uptake. CCCAs were also implanted into mice to examine their distribution in vivo. STK287794 was identified as a small molecule that induced the accumulation of lipid droplets in HDFs. CCCAs expressed adipocyte-related genes, secreted
adiponectin and
leptin, and abundantly incorporated
glucose. After implantation in mice, CCCAs resided in granulation tissue and remained adipose-like. HDFs were successfully converted into adipocytes by adding a single chemical compound, STK287794. C/EBPα and PPARγ were upregulated in STK287794-treated cells, which strongly suggests involvement of these adipocyte-related
transcription factors in the chemical direct conversion. Our method may be useful for the preparation of autogenous adipocytes for
transplantation therapy for soft tissue defects and fat tissue
atrophy.