TY - JOUR
T1 - Metabolically Active Three-Dimensional Brown Adipose Tissue Engineered from White Adipose-Derived Stem Cells
AU - Yang, Jessica P.
AU - Anderson, Amy E.
AU - McCartney, Annemarie
AU - Ory, Xavier
AU - Ma, Garret
AU - Pappalardo, Elisa
AU - Bader, Joel
AU - Elisseeff, Jennifer H.
N1 - Publisher Copyright:
© Copyright 2017, Mary Ann Liebert, Inc.
PY - 2017/4
Y1 - 2017/4
N2 - 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.
AB - 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.
KW - 3D hydrogels
KW - adipogenesis
KW - adipose-derived stem cells
KW - brown adipose tissue
KW - metabolic profiling
KW - oxygen consumption rate
UR - http://www.scopus.com/inward/record.url?scp=85018474154&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85018474154&partnerID=8YFLogxK
U2 - 10.1089/ten.tea.2016.0399
DO - 10.1089/ten.tea.2016.0399
M3 - Article
C2 - 28073315
AN - SCOPUS:85018474154
SN - 1937-3341
VL - 23
SP - 253
EP - 262
JO - Tissue Engineering - Part A
JF - Tissue Engineering - Part A
IS - 7-8
ER -