Scalable Generation of Pre-Vascularized and Functional Human Beige Adipose Organoids

Area of Science:

• Biomedical Engineering
• Metabolic Research
• Adipose Tissue Biology

Background:

• Obesity and type 2 diabetes represent significant global health challenges.
• Beige adipocytes are crucial for metabolic health but lack adequate in vitro models.
• Current research is hindered by the absence of functional human beige adipose tissue models.

Purpose of the Study:

• To engineer a scalable system for generating pre-vascularized human beige adipose tissue organoids.
• To overcome limitations of traditional bottom-up tissue engineering approaches.
• To create a reliable in vitro model for studying beige adipocytes and developing biotherapies.

Main Methods:

• Utilized human stromal vascular fraction from white adipose tissue as a source of progenitors.
• Employed a defined biomechanical and chemical environment including TGFβ pathway inhibition.
• Incorporated specific gelatin methacryloyl (GelMA) embedding parameters to promote self-organization and vascularization.
• Scaled organoid morphogenesis to centimeter-scale beige adipose micro-tissues.

Main Results:

• Generated pre-vascularized and functional human beige adipose tissue organoids.
• Organoids exhibited inducible Uncoupling Protein-1 (UCP1) expression, characteristic of beige adipocytes.
• Demonstrated increased uncoupled mitochondrial respiration and batokines secretion.
• Successfully scaled the engineered tissue to centimeter-sized micro-tissues.

Conclusions:

• The developed method provides a scalable system for creating functional human beige adipose tissue organoids.
• This advancement significantly improves in vitro modeling capabilities for beige adipose tissue research.
• Facilitates broad applications in basic research and the development of novel biotherapies for metabolic diseases.