| Yazarlar |
Mélanie Escudero
|
|
Laurence Vaysse
|
Dr. Öğr. Üyesi Gözde EKE ÇEVİK
Türkiye |
|
Marion Peyrou
|
|
Francesc Villarroya
|
|
Sophie Bonnel
|
|
Yannick Jeanson
|
|
Louisa Boyer
|
|
Christophe Vieu
|
|
Benoit Chaput
|
|
Xi Yao
|
|
Frédéric Deschaseaux
|
|
Mélissa Parny
|
|
Isabelle Raymond‐Letron
|
|
Christian Dani
|
|
Audrey Carrière
|
|
Laurent Malaquin
|
|
Louis Casteilla
|
| 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 |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale |
| Dergi Adı | ADVANCED SCIENCE |
| Dergi ISSN | 2198-3844 |
| Dergi Tarandığı Indeksler | SSCI |
| Dergi Grubu | Q1 |
| Makale Dili | İngilizce |
| Basım Tarihi | 11-2023 |
| Cilt No | 10 |
| Sayı | 31 |
| Doi Numarası | 10.1002/advs.202301499 |
| Makale Linki | http://dx.doi.org/10.1002/advs.202301499 |
| Atıf Sayıları | |
| WoS | 5 |
