Over-expression of PPAR-γ2 gene enhances the adipogenic differentiation of hemangioma-derived mesenchymal stem cells in vitro and in vivo

PPAR-γ2基因过表达促进血管瘤间充质干细胞体内外成脂分化

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作者:Si-Ming Yuan #, Yao Guo #, Qian Wang, Yuan Xu, Min Wang, Hai-Ni Chen, Wei-Min Shen

Background

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.

Conclusions

Overexpression of PPAR-γ2 gene enhances and accelerates the adipogenic differentiation of Hem-MSCs in vitro and in vivo. The results may provide the preliminary evidences for the targeted therapy of IH via PPAR-γ signal pathway.

Methods

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 in vitro. And the cells were mixed with Matrigel, then subcutaneously injected into the back of nude mice to observe the differentiation in vivo.

Results

In the in vitro 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 in vivo tests, Hem-MSCs/Matrigel plugs with overexpression of PPAR-γ2 gene also showed accelerated adipogenesis and time-phased changes of above genes. Conclusions: Overexpression of PPAR-γ2 gene enhances and accelerates the adipogenic differentiation of Hem-MSCs in vitro and in vivo. The results may provide the preliminary evidences for the targeted therapy of IH via PPAR-γ signal pathway.

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