Searching for Classical Brown Fat in Humans: Development of a Novel Human Fetal Brown Stem Cell Model. (2nd March 2016)

• Record Type: Journal Article
• Authors: Di Franco, Alessandra; Guasti, Daniele; Squecco, Roberta; Mazzanti, Benedetta; Rossi, Francesca; Idrizaj, Eglantina; Gallego-Escuredo, José M.; Villarroya, Francesc; Bani, Daniele; Forti, Gianni; Vannelli, Gabriella Barbara; Luconi, Michaela
• Is Part Of: Stem cells. Volume 34:Number 6(2016:Jun.)
• Page Start: 1679
• Page End: 1691
• Publication Date: 2016-03-02
• Subjects: Stem cells -- Adipogenesis -- UCP-1 -- Brown adipocytes -- Cell electrophysiology; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2336
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: The potential therapeutic applications of targeting brown adipose tissue open new clinical avenues in fighting against metabolic pathologies. However, due to the limited extension in adult humans of brown depots, which are dramatically reduced after birth, solid cell models to study human brown adipogenesis and its regulatory factors in pathophysiology are urgently needed. Here, we generated a novel human model of brown adipose stem cells, hfB-ASC, derived for the first time from fetal interscapular brown fat depots. Besides the characterization of their stem and classical brown adipose properties, we demonstrated that these cells retain a specific intrinsic differentiation program to functional brown adipocytes, even spontaneously generating organoid structures with brown features. Moreover, for the first time, we investigated the thermogenic and electrophysiological activity of the in vitro-derived fetal brown adipocytes compared to their undifferentiated precursors hfB-ASC, in basal and norepinephrine-induced conditions. In conclusion, from interscapular brown fat of the human fetus we developed and functionally characterized a novel physiological brown adipose stem cell model early programmed to brown differentiation, which may represent a unique opportunity for further studies on brown adipogenesis processes in humans as well as the most suitable target to study novel therapeutic approaches for stimulating brown activity in metabolic pathologies. Abstract : Electron microscopy of a mature brown adipocyte obtained by in vitro-induced adipogenesis of hfB-ASC, shows several mitochondria with the typical features found in brown adipocytes, such as rod-shape and elevated number of transversal cristae, in close proximity with two electron dense intracellular lipid droplets and endoplasmic reticulum. Scale Bar: 500 nm.