Scalable Generation of Pre‐Vascularized and Functional Human Beige Adipose Organoids
Yazarlar (18)
Mélanie Escudero Institut National de la Sante et de la Recherche Medicale (Inserm)
Laurence Vaysse Institut National de la Sante et de la Recherche Medicale (Inserm)
Dr. Öğr. Üyesi Gözde EKE ÇEVİK Kırşehir Ahi Evran Üniversitesi, Türkiye
Marion Peyrou University of Barcelona
Francesc Villarroya University of Barcelona
Sophie Bonnel Institut National de la Sante et de la Recherche Medicale (Inserm)
Yannick Jeanson Institut National de la Sante et de la Recherche Medicale (Inserm)
Louisa Boyer Universite Federale Toulouse Midi-Pyrenees (ComUE)
Christophe Vieu Universite Federale Toulouse Midi-Pyrenees (ComUE)
Benoit Chaput Universite de Toulouse
Xi Yao Institut National de la Sante et de la Recherche Medicale (Inserm)
Frédéric Deschaseaux
Mélissa Parny Institut National de la Sante et de la Recherche Medicale (Inserm)
Isabelle Raymond‐Letron Institut National de la Sante et de la Recherche Medicale (Inserm)
Christian Dani Institut National de la Sante et de la Recherche Medicale (Inserm)
Audrey Carrière Institut National de la Sante et de la Recherche Medicale (Inserm)
Laurent Malaquin Universite Federale Toulouse Midi-Pyrenees (ComUE)
Louis Casteilla Institut National de la Sante et de la Recherche Medicale (Inserm)
| Makale Türü |
Özgün Makale
(SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale)
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| Dergi Adı | ADVANCED SCIENCE (Q1) | ||
| Dergi ISSN | 2198-3844 Wos Dergi Scopus Dergi | ||
| Dergi Tarandığı Indeksler | SSCI | ||
| Makale Dili | İngilizce | Basım Tarihi | 11-2023 |
| Cilt / Sayı / Sayfa | 10 / 31 / – | DOI | 10.1002/advs.202301499 |
| Makale Linki | http://dx.doi.org/10.1002/advs.202301499 | ||
| Özet |
| 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 & beta; (TGF & beta;) 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. This study reports a scalable tissue engineering strategy to generate vascularized human beige adipose tissue (AT) constructs. Organoids and macro-scaled tissue demonstrate key functional features including cell plasticity associated with metabolic and paracrine activities adaptation specific to beige AT. This flexible system opens the way of multiple applications from basic science to biotherapies in the context of obesity and type-2 diabetes.image |
| Anahtar Kelimeler |
| adipose-derived stroma/stem cells (ASC) | beige and brown adipocytes | guided-assembly | hydrogels | microtissues | organoid morphogenesis | stromal vascular fraction |
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| Web of Science | 31 |