Metabolically Active Three-Dimensional Brown Adipose Tissue Engineered from White Adipose-Derived Stem Cells

被引:0
作者
Yang, Jessica P. [1 ]
Anderson, Amy E. [2 ]
McCartney, Annemarie [2 ]
Ory, Xavier [3 ]
Ma, Garret [1 ]
Pappalardo, Elisa [1 ,4 ]
Bader, Joel [1 ,4 ]
Elisseeff, Jennifer H. [1 ]
机构
[1] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA
[2] Johns Hopkins Univ, Dept Cellular & Mol Med, Baltimore, MD USA
[3] Ecole Polytech, Dept Biol, Palaiseau, France
[4] Johns Hopkins Univ, High Throughput Biol Ctr, Baltimore, MD USA
关键词
adipose-derived stem cells; brown adipose tissue; 3D hydrogels; adipogenesis; metabolic profiling; oxygen consumption rate; GLUCOSE-HOMEOSTASIS; FAT; ADIPOCYTES; TRANSPLANTATION; HYPOXIA; OBESITY;
D O I
10.1089/ten.tea.2016.0399
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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.
引用
收藏
页码:253 / 262
页数:10
相关论文
共 43 条
[21]   THERMOGENIC MECHANISMS IN BROWN FAT [J].
NICHOLLS, DG ;
LOCKE, RM .
PHYSIOLOGICAL REVIEWS, 1984, 64 (01) :1-64
[22]   A human-specific role of cell death-inducing DFFA (DNA fragmentation factor-α-like effector A (CIDEA) in adipocyte lipolysis and obesity [J].
Nordström, EA ;
Rydén, M ;
Backlund, EC ;
Dahlman, I ;
Kaaman, M ;
Blomqvist, L ;
Cannon, B ;
Nedergaard, J ;
Arner, P .
DIABETES, 2005, 54 (06) :1726-1734
[23]   PPARγ agonists Induce a White-to-Brown Fat Conversion through Stabilization of PRDM16 Protein [J].
Ohno, Haruya ;
Shinoda, Kosaku ;
Spiegelman, Bruce M. ;
Kajimura, Shingo .
CELL METABOLISM, 2012, 15 (03) :395-404
[24]  
Rosen ED, 2000, GENE DEV, V14, P1293
[25]   Anatomical Locations of Human trovvn Adipose Tissue Functional Relevance and Implications in Obesity and Type 2 Diabetes [J].
Sacks, Harold ;
Symonds, Michael E. .
DIABETES, 2013, 62 (06) :1783-1790
[26]   Genetic and functional characterization of clonally derived adult human brown adipocytes [J].
Shinoda, Kosaku ;
Luijten, Ineke H. N. ;
Hasegawa, Yutaka ;
Hong, Haemin ;
Sonne, Si B. ;
Kim, Miae ;
Xue, Ruidan ;
Chondronikola, Maria ;
Cypess, Aaron M. ;
Tseng, Yu-Hua ;
Nedergaard, Jan ;
Sidossis, Labros S. ;
Kajimura, Shingo .
NATURE MEDICINE, 2015, 21 (04) :389-+
[27]   Metabolically Active Human Brown Adipose Tissue Derived Stem Cells [J].
Silva, Francisco J. ;
Holt, Dolly J. ;
Vargas, Vanessa ;
Yockman, James ;
Boudina, Sihem ;
Atkinson, Donald ;
Grainger, David W. ;
Revelo, Monica P. ;
Sherman, Warren ;
Bull, David A. ;
Patel, Amit N. .
STEM CELLS, 2014, 32 (02) :572-581
[28]   Modular Multifunctional Poly(ethylene glycol) Hydrogels for Stem Cell Differentiation [J].
Singh, Anirudha ;
Zhan, Jianan ;
Ye, Zhaoyang ;
Elisseeff, Jennifer H. .
ADVANCED FUNCTIONAL MATERIALS, 2013, 23 (05) :575-582
[29]   Brown adipose tissue regulates glucose homeostasis and insulin sensitivity [J].
Stanford, Kristin I. ;
Middelbeek, Roeland J. W. ;
Townsend, Kristy L. ;
An, Ding ;
Nygaard, Eva B. ;
Hitchcox, Kristen M. ;
Markan, Kathleen R. ;
Nakano, Kazuhiro ;
Hirshman, Michael F. ;
Tseng, Yu-Hua ;
Goodyear, Laurie J. .
JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (01) :215-223
[30]   Mir193b-365 is essential for brown fat differentiation [J].
Sun, Lei ;
Xie, Huangming ;
Mori, Marcelo A. ;
Alexander, Ryan ;
Yuan, Bingbing ;
Hattangadi, Shilpa M. ;
Liu, Qingqing ;
Kahn, C. Ronald ;
Lodish, Harvey F. .
NATURE CELL BIOLOGY, 2011, 13 (08) :958-U198