Yuan Si-Ming, Guo Yao, Wang Qian, Xu Yuan, Wang Min, Chen Hai-Ni, Shen Wei-Min
Department of Plastic Surgery and Vascular Biology Lab, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, China.
Department of Plastic Surgery, Children's Hospital, Nanjing, Jiangsu 210008, China.
Oncotarget. 2017 Dec 26;8(70):115817-115828. doi: 10.18632/oncotarget.23705. eCollection 2017 Dec 29.
Most of infantile hemangiomas involute into fibrofatty tissue in childhood, which indicates adipogenesis during this period. Mesenchymal stem cells (MSCs) contribute to the adipogenesis in IH. In this study, we investigated the effects of overexpression of PPAR-γ2 gene on the adipogenic differentiation of Hemangioma-derived MSCs (Hem-MSCs), and discussed the possibility of targeted therapy via PPAR-γ pathway.
MSCs were isolated from proliferating hemangioma by their selective adhesion to plastic culture dishes. Recombinant lentivirus with PPAR-γ2 gene were prepared, and used to transfect Hem-MSCs. Transfected cells were cultured in adipogenic medium to observe the differentiation . And the cells were mixed with Matrigel, then subcutaneously injected into the back of nude mice to observe the differentiation .
In the tests, Hem-MSCs with overexpression of PPAR-γ2 gene showed enhanced adipogenic differentiation with increased expression of adipogenic-related genes, including PPAR-γ2, ADD1, LPL, and CEBPA genes. In the tests, Hem-MSCs/Matrigel plugs with overexpression of PPAR-γ2 gene also showed accelerated adipogenesis and time-phased changes of above genes.
Overexpression of PPAR-γ2 gene enhances and accelerates the adipogenic differentiation of Hem-MSCs and . The results may provide the preliminary evidences for the targeted therapy of IH via PPAR-γ signal pathway.
大多数婴儿血管瘤在儿童期会 involute 为纤维脂肪组织,这表明在此期间发生了脂肪生成。间充质干细胞(MSCs)参与了婴儿血管瘤中的脂肪生成。在本研究中,我们研究了过表达 PPAR-γ2 基因对血管瘤来源的间充质干细胞(Hem-MSCs)脂肪生成分化的影响,并探讨了通过 PPAR-γ 途径进行靶向治疗的可能性。
通过间充质干细胞对塑料培养皿的选择性黏附,从增殖期血管瘤中分离出间充质干细胞。制备携带 PPAR-γ2 基因的重组慢病毒,并用于转染 Hem-MSCs。将转染后的细胞在成脂培养基中培养以观察分化情况。并且将细胞与基质胶混合,然后皮下注射到裸鼠背部以观察分化情况。
在 测试中,过表达 PPAR-γ2 基因的 Hem-MSCs 显示出增强的脂肪生成分化,成脂相关基因的表达增加,包括 PPAR-γ2、ADD1、LPL 和 CEBPA 基因。在 测试中,过表达 PPAR-γ2 基因的 Hem-MSCs/基质胶栓也显示出加速的脂肪生成以及上述基因的时间阶段性变化。
过表达 PPAR-γ2 基因增强并加速了 Hem-MSCs 和 的脂肪生成分化。这些结果可能为通过 PPAR-γ 信号通路对婴儿血管瘤进行靶向治疗提供初步证据。