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

Area of Science:

• Biotechnology
• Metabolic Engineering
• Stem Cell Biology

Background:

• Brown adipose tissue (BAT) expends calories, offering therapeutic potential for obesity and type 2 diabetes.
• Existing therapies require methods to supplement limited adult human brown adipocytes.
• Engineering ex vivo BAT constructs is crucial for therapeutic applications.

Purpose of the Study:

• To engineer functional brown adipose tissue (BAT) from human and rat adipose precursors.
• To assess if ex vivo engineered BAT constructs mimic in vivo tissue form and metabolic function.
• To explore the therapeutic potential of engineered BAT for metabolic diseases.

Main Methods:

• Isolated adipose-derived stem cells (ASCs) from human and rat white adipose tissue (WAT) and BAT.
• Differentiated ASCs towards white and brown adipogenic lineages in 2D and 3D cultures.
• Utilized 3D poly(ethylene glycol) hydrogels for adipocyte differentiation and tissue engineering.

Main Results:

• Successfully differentiated WAT-derived ASCs into mature adipocytes with a BAT phenotype in 3D hydrogels.
• Engineered adipocytes exhibited high uncoupling protein 1 (UCP1) mRNA and protein expression.
• Demonstrated increased metabolic activity, including oxygen consumption and proton leak, characteristic of functional BAT.

Conclusions:

• White adipose tissue stem cells can be engineered into 3D tissue constructs with BAT metabolic capacity.
• This
• browning
• process enables the creation of functional BAT for therapeutic intervention.
• Engineered BAT serves as a valuable tool for studying BAT function and metabolic properties.