Direct Conversion of Human Fibroblasts into Adipocytes Using a Novel Small Molecular Compound: Implications for Regenerative Therapy for Adipose Tissue Defects

Abstract

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.

Topical Simvastatin Improves Lesions of Diffuse Normolipemic Plane Xanthoma by Inhibiting Foam Cell Pyroptosis

“…However, our results were only validated in foam cells. Any one of these cells may also play an important role in the pathogenesis of DNPX, as previous literatures reported that skin fibroblasts can transform to fat cells under certain conditions ( 44 ). In addition, our results indicated the existence of an interaction between NLRP3 and HMGCR.…”

Rapid direct conversion of bovine non-adipogenic fibroblasts into adipocyte-like cells by a small-molecule cocktail

“…The adipocytes were observed for 10–15 days ( Zhu et al, 2012 ). Afterwards, Sowa et al (2021 ) revealed that human dermal fibroblasts can be directly converted into adipocytes by adding a single chemical compound, STK287794, for 14 days. Moreover, Xie’s team reported that RepSox in the fibroblast growth medium (MDI free) for 10 days was sufficient to induce adipogenesis in MEFs ( Tu et al, 2019 ).…”

“…Furthermore, small-molecule compound induction is expected to be a novel approach to generate new cell types from somatic cells in vitro and in vivo ( Kim et al, 2020 ). Previous studies have shown the direct conversion of fibroblasts [human ( Takeda et al, 2017 ; Sowa et al, 2021 ), mouse ( Tu et al, 2019 ), and pig ( Zhu et al, 2012 )] into adipocytes using small-molecular compounds. Until now, it has not been well characterized yet about the mechanism of adipose differentiation by transdifferentiation of bovine fibroblasts into adipocyte using small chemical molecules.…”

Multi-Probiotic Lactobacillus Supplementation Improves Liver Function and Reduces Cholesterol Levels in Jeju Native Pigs

“…Chemerin plays a significant role in glucose metabolism, obesity, insulin resistance, adipose tissue inflammation, and liver pathology [ 20 ]. Adiponectin is exclusively secreted from adipose tissue, and it acts as an autocrine factor in adipose tissues, promoting cell proliferation and differentiation of pre-adipocytes to mature adipocytes [ 21 ]. An important finding of this study is that dietary Lactobacillus supplementation significantly reduced blood cholesterol concentration as well as adiponectin and chemerin secretion from adipose tissues.…”