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.
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.
Authors: John S K Yuen; Andrew J Stout; N Stephanie Kawecki; Sophia M Letcher; Sophia K Theodossiou; Julian M Cohen; Brigid M Barrick; Michael K Saad; Natalie R Rubio; Jaymie A Pietropinto; Hailey DiCindio; Sabrina W Zhang; Amy C Rowat; David L Kaplan Journal: Biomaterials Date: 2021-11-29 Impact factor: 15.304