Metabolically Active Human Brown Adipose Tissue Derived Stem Cells

Abstract

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 mm 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. STEM CELLS 2014;32:572-581

Effects of autologous adipose-derived stem cell infusion on type 2 diabetic rats

“…In the present study, we induced T2DM in a rat model by a high-fat diet combined with STZ administration and performed ASC infusion at the 28 th day after STZ injection. We found that ASC infusion could effectively ameliorate hyperglycemia in T2DM rats, which was consistent with other reports [1,2,23]. Furthermore, our results of hyperinsulinemic-euglycemic clamp studies demon-INSR in skeletal muscle and adipose and liver tissues after therapy to investigate the possible mechanisms involved in the effect of ASC infusion on insulin sensitivity.…”

“…ASC can be isolated from small amounts of adipose tissue, efficiently expanded to achieve a very large number after 3 to 4 passages, and have the advantage of low immunogenicity and high multipotency. Their immunmodulatory function, homing and migratory patterns, as well as previous clinical trials, have suggested that these cells are efficient and safe for treating several classes of autoimmune diseases [1][2][3][4].…”

Human Brown Adipose Tissue: What We Have Learned So Far

“…Recently, a role for alternatively activated macrophages and eosinophils in the development of functional beige BAT has been reported in mice (57,58). Additionally, a population of brown adipocyte progenitors was identified in skeletal muscle in both mice (59) and humans (60,61). These cells could be differentiated into mature brown adipocytes by stimulation with bone morphogenetic protein (BMP) 7, thus presenting a potential target for pharmacological intervention in humans.…”

Transplantation of Adipose-Derived Stem Cells in Stroke

“…On the other hand, specific origins of ADSC may also be taken into account for special therapeutic needs. For instance, a clonogenic population of metabolically active stem cells has been reported to reside in adult human brown adipose tissue that may be activated to participate in energy homeostasis in vivo and, therefore, may be of therapeutic importance for obesity and related metabolic disorders (Silva et al 2014).…”