Open AccessMetabolically Active Human Brown Adipose Tissue Derived Stem Cells
Author(s) -
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.
Publication year - 2014
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1595
Subject(s) - biology , stem cell , brown adipose tissue , multipotent stem cell , progenitor cell , microbiology and biotechnology , population , thermogenesis , adipose tissue , adult stem cell , induced pluripotent stem cell , immunology , endocrinology , endothelial stem cell , in vitro , embryonic stem cell , biochemistry , demography , sociology , gene
Brown adipose tissue (BAT) plays a key role in the evolutionarily conserved mechanisms underlying energy homeostasis in mammals. It is characterized by fat vacuoles 5–10 µm in diameter and expression of uncoupling protein one, central to the regulation of thermogenesis. In the human newborn, BAT depots are typically grouped around the vasculature and solid organs. These depots maintain body temperature during cold exposure by warming the blood before its distribution to the periphery. They also ensure an optimal temperature for biochemical reactions within solid organs. BAT had been thought to involute throughout childhood and adolescence. Recent studies, however, have confirmed the presence of active BAT in adult humans with depots residing in cervical, supraclavicular, mediastinal, paravertebral, and suprarenal regions. While human pluripotent stem cells have been differentiated into functional brown adipocytes in vitro and brown adipocyte progenitor cells have been identified in murine skeletal muscle and white adipose tissue, multipotent metabolically active BAT‐derived stem cells from a single depot have not been identified in adult humans to date. Here, we demonstrate a clonogenic population of metabolically active BAT stem cells residing in adult humans that can: (a) be expanded in vitro; (b) exhibit multilineage differentiation potential; and (c) functionally differentiate into metabolically active brown adipocytes. Our study defines a new target stem cell population that can be activated to restore energy homeostasis in vivo for the treatment of obesity and related metabolic disorders. S tem C ells 2014;32:572–581