hiPSC-derived Adipoids: Scalable Human Adipose Tissue Model

bioRxiv (Biozentrum, University of Basel) Switzerland

Overview

Researchers have developed “adipoids,” three-dimensional microtissues derived from human induced pluripotent stem cells (hiPSCs) that mimic functional human adipose tissue. These adipoids exhibit long-term stability and viability, providing a scalable and genetically tractable platform for pharmacological screening and metabolic disease research.

In Depth

Key Findings

The study introduces a protocol for generating functional, three-dimensional human induced pluripotent stem cell (hiPSC)-derived adipocyte microtissues, referred to as adipoids. These adipoids demonstrate long-term stability and viability, offering a scalable alternative to traditional adipose tissue models. Functional analysis confirms that these microtissues contain unilocular adipocytes, secrete adipokines, and exhibit stimulated lipolysis.

Technical Details

To characterize the composition of the adipoids, the researchers employed single-nucleus RNA sequencing. The results revealed that the adipoids consist of both mature adipocytes and adipocyte stem/progenitor cells, a composition that closely resembles native human adipose tissue. This structural and cellular similarity ensures that the model maintains the biological characteristics necessary for high-fidelity metabolic research.

Background and Context

Human adipose tissue models are critical for studying metabolic research, yet existing methods have significant limitations. Traditional primary cell cultures lack scalability and are unsuitable for large-scale drug screening or the modeling of genetic diseases. Furthermore, conventional two-dimensional (2D) adipocyte cultures are unable to withstand the long-term treatments required to simulate chronic metabolic conditions, such as insulin resistance and obesity.

Significance and Outlook

The development of hiPSC-derived adipoids addresses the shortcomings of 2D cultures and primary cells by providing a functional and genetically tractable model. Because they are scalable and stable over long periods, these adipoids are positioned as a viable tool for performing large-scale pharmacological screens and investigating the mechanisms of human metabolic diseases.

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