Oncotarget

Research Papers:

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

Si-Ming Yuan _, Yao Guo, Qian Wang, Yuan Xu, Min Wang, Hai-Ni Chen and Wei-Min Shen

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Oncotarget. 2017; 8:115817-115828. https://doi.org/10.18632/oncotarget.23705

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Abstract

Si-Ming Yuan1,*, Yao Guo1,*, Qian Wang1, Yuan Xu1, Min Wang1, Hai-Ni Chen2 and Wei-Min Shen2

1Department of Plastic Surgery and Vascular Biology Lab, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, China

2Department of Plastic Surgery, Children’s Hospital, Nanjing, Jiangsu 210008, China

*These authors have contributed equally to this work

Correspondence to:

Si-Ming Yuan, email: [email protected]

Keywords: infantile hemangioma; involution; mesenchymal stem cell; PPAR-γ; adipogenesis

Received: August 08, 2017     Accepted: December 05, 2017     Published: December 26, 2017

ABSTRACT

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.

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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