Direct Conversion of Human Fibroblasts into Adipocytes Using a Novel Small Molecular Compound: Implications for Regenerative Therapy for Adipose Tissue Defects.
Direct Conversion of Human Fibroblasts into Adipocytes Using a Novel Small Molecular Compound: Implications for Regenerative Therapy for Adipose Tissue Defects.
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DOI：
10.3390/cells10030605
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发表时间：
2021-03-09
期刊：
影响因子：
6
通讯作者：
Mazda O
中科院分区：
文献类型：
--
作者：
Sowa Y;Kishida T;Louis F;Sawai S;Seki M;Numajiri T;Takahashi K;Mazda O
在整形外科中需要制备自体脂肪细胞，其可以移植到患者体内以重建由肿瘤切除（包括乳腺癌）以及由创伤和其他疾病引起的软组织缺损。将体细胞直接转化为脂肪细胞可以获得足够的功能性脂肪细胞用于再生治疗。筛选了10，800个分子的化学文库诱导培养的人真皮成纤维细胞（HDF）中脂质积累的能力。通过脂质染色、免疫染色和qRT-PCR表征化学化合物介导的直接转化的脂肪细胞（CCCA），并检测脂肪因子分泌和葡萄糖摄取。还将CCCA植入小鼠体内以检查其体内分布。STK 287794被鉴定为诱导HDF中脂滴积聚的小分子。CCCA表达脂肪细胞相关基因，分泌脂联素和瘦素，并大量掺入葡萄糖。在小鼠体内植入后，CCCA驻留在肉芽组织中并保持脂肪样。通过添加单一化合物STK 287794，将HDF成功转化为脂肪细胞。C/EBPα和PPARγ在STK 287794处理的细胞中上调，这强烈表明这些脂肪细胞相关转录因子参与了化学直接转化。我们的方法可能是有用的制备自体脂肪细胞移植治疗软组织缺损和脂肪组织萎缩。
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.
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影响因子：
3.6
作者：
Hong, Ki Yong;Yim, Sangjun;Minn, Kyung Won
通讯作者：
Minn, Kyung Won
影响因子：
50.3
作者：
Ishay-Ronen, Dana;Diepenbruck, Maren;Christofori, Gerhard
通讯作者：
Christofori, Gerhard
影响因子：
10.5
作者：
Rosen, ED;Hsu, CH;Spiegelman, BM
通讯作者：
Spiegelman, BM
影响因子：
--
作者：
Basu-Roy U;Han E;Rattanakorn K;Gadi A;Verma N;Maurizi G;Gunaratne PH;Coarfa C;Kennedy OD;Garabedian MJ;Basilico C;Mansukhani A
通讯作者：
Mansukhani A
影响因子：
3.7
作者：
Lessard J;Pelletier M;Biertho L;Biron S;Marceau S;Hould FS;Lebel S;Moustarah F;Lescelleur O;Marceau P;Tchernof A
通讯作者：
Tchernof A