Scalable Generation of Pre-Vascularized and Functional Human Beige Adipose Organoids.
adipose-derived stroma/stem cells (ASC)
beige and brown adipocytes
guided-assembly
hydrogels
microtissues
organoid morphogenesis
stromal vascular fraction
Journal
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
revised:
07
08
2023
received:
07
03
2023
medline:
6
11
2023
pubmed:
21
9
2023
entrez:
21
9
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37731092
doi: 10.1002/advs.202301499
pmc: PMC10625054
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2301499Subventions
Organisme : Agence Nationale de la Recherche
ID : ANR-18-CE18-0006
Organisme : Agence Nationale de la Recherche
ID : ANR21 CE1941
Organisme : Agence Nationale de la Recherche
ID : 18-EURE-0003
Organisme : LAAS-CNRS micro and nanotechnologies platform
Organisme : MultiFAB project
ID : 16007407/MP0011594
Organisme : HoliFAB project
ID : 760927
Organisme : HoliFAB project
ID : PID2020-114112RB-I00
Organisme : MCIN/AEI/10.13039/501100011033, Spain and the European Regional Development Fund
ID : PID2020-114112RB-I00
Informations de copyright
© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.
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