Engineered Brown Fat For Metabolic Disorders


BioRestorative Therapies, Inc, (BRTX) has announced what they termed as “promising data” on the transplantation of human stem cell-derived tissue engineering from brown fat.

This study is in a meeting abstract at the moment, so there is no paper to reference at the time. The presentation entitled, “In Vitro Evaluation of an Encapsulation System for the Transplantation of Human Stem Cell-Derived Tissue Engineered Brown Fat,” was given at the International Society for Cellular Therapy meeting in Singapore.

In a nutshell, BRTX scientists examined a technique in which they isolated brown fat-derived stem cell populations, and then differentiated those cells in a step-wide fashion into three-dimensional brown fat assemblages. These brown fat constructs were loaded into tiny microcapsules that can potentially deliver these cells into the tissues of a living organism.

Brown fat cells possess a protein called UCP-1 (Uncoupling Protein-1). This protein short circuits the energy producing machinery of cells and converts that energy into heat instead of the energy-storing molecule ATP. Thus, brown fat cells burn more calories than show regular fat cells and generate a good deal more heat. Increasing brown fat levels in a patient with a weight problem could, in theory, at least, cause that patient to inherently burn more calories.

The laboratory-derived, encapsulated brown fat cells seemed to excellent survival and also expressed respectable amounts of UCP-1.

BRTX would like to, someday, transplant these encapsulated cells into human patients someday, but before that day comes, a good deal of animal experiments are required to demonstrate the safety and efficacy of this product. Then and only then will human experiments be warranted.

Brown Fat Stem Cells for Treating Diabetes and Obesity


Mammals have two main types of fat: brown fat and white fat.  Brown fat is especially abundant in newborns and in mammals undergoing hibernation.  The primary function of brown fat is to produce body heat so that the animal does not shiver.  In contrast to white fat cells, which contain a single lipid droplet, brown fat cells contain numerous smaller droplets and a higher number of mitochondria, and it is these mitochondria and their high iron content that makes this fat tissue brown.  Brown fat also contains more small blood vessels than white fat, since it has a greater need for oxygen than most tissues.

Recently, researchers at the University of Utah School of Medicine have identified stem cells from brown fat.  The principal researcher of this project, Amit Patel, associate professor of medicine, refuted an old dogma – that adult humans do not possess brown fat.  Children have large amounts of brown fat that is highly metabolically active.  Children can eat a great deal and not gain any weight, relative to adults.  Adults, on the other hand, have an abundance of white fat, and accumulation of white fat leads to weight gain and cardiovascular disease (something not seen in brown fat).  As people age, the amount of white fat increases and the amount of brown fat decreases, which contributes to the onset of diabetes and high cholesterol.

As Patel put it, “If you have more brown fat, you weigh less, you’re metabolically efficient, and you have fewer instances of diabetes and high cholesterol.  The unique identification of human brown fat stem cells in the chest of patients aged 28-34 years is profound.  We were able to isolate the human stem cells, culture and grow them, and implant them into a pre-human model which has demonstrated positive effects on glucose levels.”

In vitro differentiation of brown adipose derived stem cells (BADSCs). (A) Gene expression profile comparing undifferentiated BADSCs to undifferentiated white adipose derived stem cells derived from subcutaneous adipose tissue. Genes in red are associated with brown fat phenotype. (B) Gene expression profile comparing undifferentiated brown adipose derived stem cells to differentiated brown adipocytes. Biological replicates performed in triplicate from a single clone were used for gene expression profile. (C) Transmission electron microscopy of 21 day brown adipocyte differentiation induced with fibronectin type III domain containing 5 (FNDC5) demonstrate multiocular intracytoplasmic lipid vacuoles and mitochondria (arrows). (D) Alizarian red staining of brown adipose derived stem cells induced to undergo osteogenesis. (E) Alcian blue staining of brown adipose derived stem cells directionally differentiated into chondrocytes. (F) Fatty acid binding protein 4 (FABP4) immunocytochemistry of brown adipose derived stem cells induced to undergo white adipogenesis. (G) Undifferentiated BADSCs. (H) Western blot 21 days post FNDC5 induction. Lane 1 brown adipose derived stem cells directionally differentiated into brown adipocytes. Lane 2 non- FNDC5 cells.
In vitro differentiation of brown adipose derived stem cells (BADSCs). (A) Gene expression
profile comparing undifferentiated BADSCs to undifferentiated white adipose derived stem cells
derived from subcutaneous adipose tissue. Genes in red are associated with brown fat phenotype. (B)
Gene expression profile comparing undifferentiated brown adipose derived stem cells to differentiated
brown adipocytes. Biological replicates performed in triplicate from a single clone were used for gene
expression profile. (C) Transmission electron microscopy of 21 day brown adipocyte differentiation
induced with fibronectin type III domain containing 5 (FNDC5) demonstrate multiocular
intracytoplasmic lipid vacuoles and mitochondria (arrows). (D) Alizarian red staining of brown
adipose derived stem cells induced to undergo osteogenesis. (E) Alcian blue staining of brown adipose
derived stem cells directionally differentiated into chondrocytes. (F) Fatty acid binding protein 4
(FABP4) immunocytochemistry of brown adipose derived stem cells induced to undergo white
adipogenesis. (G) Undifferentiated BADSCs. (H) Western blot 21 days post FNDC5 induction. Lane 1
brown adipose derived stem cells directionally differentiated into brown adipocytes. Lane 2 non-
FNDC5 cells.

This new discovery of finding brown fat stem cells may help in identifying potential drugs that may increase the body’s own ability to make brown fat or find novel ways to directly implant brown fat stem cells into patients.