title: Metabolically Active Three-Dimensional Brown Adipose Tissue Engineered from White Adipose-Derived Stem Cells.
abstract: Brown adipose tissue (BAT) has a unique capacity to expend calories by decoupling energy expenditure from ATP production, therefore BAT could realize therapeutic potential to treat metabolic diseases such as obesity and type 2 diabetes. Recent studies have investigated markers and function of native BAT, however, successful therapies will rely on methods that supplement the small existing pool of brown adipocytes in adult humans. In this study, we engineered BAT from both human and rat adipose precursors and determined whether these ex vivo constructs could mimic in vivo tissue form and metabolic function. Adipose-derived stem cells (ASCs) were isolated from several sources, human white adipose tissue (WAT), rat WAT, and rat BAT, then differentiated toward both white and brown adipogenic lineages in two-dimensional and three-dimensional (3D) culture conditions. ASCs derived from WAT were successfully differentiated in 3D poly(ethylene glycol) hydrogels into mature adipocytes with BAT phenotype and function, including high uncoupling protein 1 (UCP1) mRNA and protein expression and increased metabolic activity (basal oxygen consumption, proton leak, and maximum respiration). By utilizing this "browning" process, the abundant and accessible WAT stem cell population can be engineered into 3D tissue constructs with the metabolic capacity of native BAT, ultimately for therapeutic intervention in vivo and as a tool for studying BAT and its metabolic properties.
authors.affiliation: 1 Translational Tissue Engineering Center and Department of Biomedical Engineering, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Jessica P
authors.initials: JP
authors.lastname: Yang
authors.affiliation: 2 Translational Tissue Engineering Center and Department of Cellular and Molecular Medicine, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Anderson
authors.affiliation: 2 Translational Tissue Engineering Center and Department of Cellular and Molecular Medicine, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Annemarie
authors.initials: A
authors.lastname: McCartney
authors.affiliation: 3 Department of Biology, Ecole Polytechnique , Palaiseau, France .
authors.forename: Xavier
authors.initials: X
authors.lastname: Ory
authors.affiliation: 1 Translational Tissue Engineering Center and Department of Biomedical Engineering, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Garret
authors.initials: G
authors.lastname: Ma
authors.affiliation: 4 Department of Biomedical Engineering and High-Throughput Biology Center, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Elisa
authors.initials: E
authors.lastname: Pappalardo
authors.affiliation: 4 Department of Biomedical Engineering and High-Throughput Biology Center, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Joel
authors.initials: J
authors.lastname: Bader
authors.affiliation: 1 Translational Tissue Engineering Center and Department of Biomedical Engineering, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Elisseeff
mesh_terms: D050156:Adipogenesis / Q000502:physiology; D000273:Adipose Tissue / Q000166:cytology*; D002001:Adipose Tissue, Brown / Q000166:cytology*; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods*
keywords: 3D hydrogels; adipogenesis; adipose-derived stem cells; brown adipose tissue; metabolic profiling; oxygen consumption rate