Reproducing human fat tissue in the laboratory? This is now possible thanks to a research team bringing together Inserm, CNRS, Toulouse III-Paul-Sabatier University, the French Blood Establishment and the Toulouse National Veterinary School (ENVT) within the STROMALab laboratory. This team has developed – via 3-dimensional culture – small cellular units that mimic the characteristics and organization of adipose tissue as it appears in vivo: the organoids of adipose tissue or « adipospheres ». In their article in Scientific Reports, the researchers detail the different stages of the experimental conditions necessary to obtain these adipospheres from human cells. This innovation could make it possible, in particular, to study pathologies associated with the dysfunction of this tissue such as obesity and type 2 diabetes, but also to develop new drugs to treat these diseases.
Human adipose tissue, richly vascularized by a network of capillaries, consists of fat cells called « adipocytes ». Until now, to study it in the laboratory, researchers have been working on 2D models that do not reflect the 3D architecture of this tissue, as found in the human body.
« Mini organs » called « organoids », capable of reproducing the cellular organization of a specific organ, had already been developed for certain tissues such as that of the intestine. However, there were no such devices available to reproduce the 3D cellular and vascular organization of fat tissue in the laboratory.
This has now been done thanks to researchers from Inserm, CNRS, Toulouse III-Paul-Sabatier University, the French Blood Establishment and the National Veterinary School of Toulouse, who have joined forces in the STROMALab laboratory. Thanks to the advent of new 3D cell culture methods, the control of the selection and characterization of stromal cells in adipose tissue (support cells), this team has been able to develop organoids of this tissue, called « adipospheres ».
Generation of organoids in 3D
Using these stromal cells from human adipose tissue, the researchers developed new conditions for culture in 2D and then in 3D, making it possible to obtain both adipocytes and endothelial cells from this tissue. The resulting adipospheres contained an intact vascular network organized around adipocytes in a manner identical to that of the actual human tissue. Better still, the resulting fat cells were able to differentiate into brown or white tissue fat cells (the two types of fat tissue in humans) in the same way as those found in the human body.
The research team then transplanted these adipospheres into mice to check the functionality of their vascular network. They found that not only was this network maintained in the body, but it had also expanded by making connections to the host’s circulatory system.
The researchers also observed so-called « chimeric » vessels, made up of both mouse and human cells. « All these elements are signs of the host’s good tolerance towards transplanted organoids, explain Isabelle Ader, INSERM researcher, and Frédéric Deschaseaux, from the French Blood Establishment, authors of the study. This leads to the conclusion that not only are these small structures faithful to the organization of human tissue, but that they are also able to maintain themselves alive through connections to the circulatory system of the host that provides them with oxygen and necessary nutrients. »
According to the researchers, this innovation will make it possible to continue studies on the functioning and properties of adipose tissue in humans, thus reducing the use of animals and working directly on human tissue.
« This innovation will also make it possible to test different drugs that could be used to treat certain diseases related to adipose tissue pathology such as obesity or type 2 diabetes, » conclude Isabelle Ader and Frédéric Deschaseaux.
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Article in Le quotidien du médecin