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Published on: March 28, 2013
Transient overexpression of Pparγ2 and C/ebpα in mesenchymal stem cells induces brown adipose tissue formation
Dmitriy Sheyn1, Gadi Pelled, Wafa Tawackoli
1Skeletal Biotech Laboratory, Hebrew University-Hadassah, Faculty of Dental Medicine, Jerusalem, Israel.
Background:
Brown adipose tissue plays a pivotal role in mammal metabolism and thermogenesis. It has a great therapeutic potential in several metabolic disorders such as obesity and diabetes. Mesenchymal stem cells (MSCs) are suitable candidates for brown adipose tissue formation de novo. Pparγ2 and C/ebpα are nucleic receptors known to mediate adipogenic differentiation. We hypothesized that overexpression of the Pparγ2 and C/ebpα genes in MSCs would lead to the formation of adipose tissue.
Materials & Methods:
MSCs bearing the Luc reporter gene were transfected to overexpress Pparγ2 and C/ebpα. Differentiation of nucleofected cells was evaluated in vitro and in vivo following ectopic implantation of the cells in C3H/HeN mice.
Results:
After implantation, the engineered cells survived for 5 weeks and brown adipose-like tissue was observed in histological samples. Immunostaining and bioluminescent imaging showed new adipocytes expressing Luc and the brown adipose tissue marker, UCP1, in vitro and in vivo.
Conclusion:
We show that gene delivery of transcription factors into MSCs generates brown adipose tissue in vitro and in vivo.
