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

Autor: Escudero M; RESTORE Research Center, Université de Toulouse, INSERM 1301, CNRS 5070, EFS, ENVT, Toulouse, 31100, France.; LAAS-CNRS, Université de Toulouse, CNRS, INSA, Toulouse, 31400, France., Vaysse L; RESTORE Research Center, Université de Toulouse, INSERM 1301, CNRS 5070, EFS, ENVT, Toulouse, 31100, France., Eke G; LAAS-CNRS, Université de Toulouse, CNRS, INSA, Toulouse, 31400, France., Peyrou M; CIBER 'Fisiopatologia de la Obesidad y Nutrición', Department of Biochemistry and Molecular Biomedicine, University of Barcelona, Madrid, 28029, Spain., Villarroya F; CIBER 'Fisiopatologia de la Obesidad y Nutrición', Department of Biochemistry and Molecular Biomedicine, University of Barcelona, Madrid, 28029, Spain., Bonnel S; RESTORE Research Center, Université de Toulouse, INSERM 1301, CNRS 5070, EFS, ENVT, Toulouse, 31100, France., Jeanson Y; RESTORE Research Center, Université de Toulouse, INSERM 1301, CNRS 5070, EFS, ENVT, Toulouse, 31100, France., Boyer L; LAAS-CNRS, Université de Toulouse, CNRS, INSA, Toulouse, 31400, France., Vieu C; LAAS-CNRS, Université de Toulouse, CNRS, INSA, Toulouse, 31400, France., Chaput B; Service de Chirurgie plastique, reconstructrice et esthétique, Centre Hospitalier Universitaire Rangueil, Toulouse, 31400, France., Yao X; Faculté de Médecine, Université Côte d'Azur, INSERM, CNRS, iBV, Nice, 06103, France., Deschaseaux F; RESTORE Research Center, Université de Toulouse, INSERM 1301, CNRS 5070, EFS, ENVT, Toulouse, 31100, France., Parny M; RESTORE Research Center, Université de Toulouse, INSERM 1301, CNRS 5070, EFS, ENVT, Toulouse, 31100, France.; LabHPEC, Histology and Pathology Department, Université de Toulouse, ENVT, Toulouse, 31076, France., Raymond-Letron I; RESTORE Research Center, Université de Toulouse, INSERM 1301, CNRS 5070, EFS, ENVT, Toulouse, 31100, France.; LabHPEC, Histology and Pathology Department, Université de Toulouse, ENVT, Toulouse, 31076, France., Dani C; Faculté de Médecine, Université Côte d'Azur, INSERM, CNRS, iBV, Nice, 06103, France., Carrière A; RESTORE Research Center, Université de Toulouse, INSERM 1301, CNRS 5070, EFS, ENVT, Toulouse, 31100, France., Malaquin L; LAAS-CNRS, Université de Toulouse, CNRS, INSA, Toulouse, 31400, France., Casteilla L; RESTORE Research Center, Université de Toulouse, INSERM 1301, CNRS 5070, EFS, ENVT, Toulouse, 31100, France.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2023 Nov; Vol. 10 (31), pp. e2301499. Date of Electronic Publication: 2023 Sep 20.
DOI: 10.1002/advs.202301499
Abstrakt: Obesity and type 2 diabetes are becoming a global sociobiomedical burden. Beige adipocytes are emerging as key inducible actors and putative relevant therapeutic targets for improving metabolic health. However, in vitro models of human beige adipose tissue are currently lacking and hinder research into this cell type and biotherapy development. Unlike traditional bottom-up engineering approaches that aim to generate building blocks, here a scalable system is proposed to generate pre-vascularized and functional human beige adipose tissue organoids using the human stromal vascular fraction of white adipose tissue as a source of adipose and endothelial progenitors. This engineered method uses a defined biomechanical and chemical environment using tumor growth factor β (TGFβ) pathway inhibition and specific gelatin methacryloyl (GelMA) embedding parameters to promote the self-organization of spheroids in GelMA hydrogel, facilitating beige adipogenesis and vascularization. The resulting vascularized organoids display key features of native beige adipose tissue including inducible Uncoupling Protein-1 (UCP1) expression, increased uncoupled mitochondrial respiration, and batokines secretion. The controlled assembly of spheroids allows to translate organoid morphogenesis to a macroscopic scale, generating vascularized centimeter-scale beige adipose micro-tissues. This approach represents a significant advancement in developing in vitro human beige adipose tissue models and facilitates broad applications ranging from basic research to biotherapies.
(© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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