Scalable Generation of Pre‐Vascularized and Functional Human Beige Adipose Organoids
Abstract 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 r...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-11-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202301499 |
| _version_ | 1797637395248578560 |
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| author | Mélanie Escudero Laurence Vaysse Gozde Eke 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 |
| author_facet | Mélanie Escudero Laurence Vaysse Gozde Eke 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 |
| author_sort | Mélanie Escudero |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-11T12:47:48Z |
| format | Article |
| id | doaj.art-83470d91099c4eaf88a947e0c14bbee6 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-11T12:47:48Z |
| publishDate | 2023-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-83470d91099c4eaf88a947e0c14bbee62023-11-04T08:56:52ZengWileyAdvanced Science2198-38442023-11-011031n/an/a10.1002/advs.202301499Scalable Generation of Pre‐Vascularized and Functional Human Beige Adipose OrganoidsMélanie Escudero0Laurence Vaysse1Gozde Eke2Marion Peyrou3Francesc Villarroya4Sophie Bonnel5Yannick Jeanson6Louisa Boyer7Christophe Vieu8Benoit Chaput9Xi Yao10Frédéric Deschaseaux11Mélissa Parny12Isabelle Raymond‐Letron13Christian Dani14Audrey Carrière15Laurent Malaquin16Louis Casteilla17RESTORE Research Center Université de Toulouse, INSERM 1301, CNRS 5070, EFS, ENVT Toulouse 31100 FranceRESTORE Research Center Université de Toulouse, INSERM 1301, CNRS 5070, EFS, ENVT Toulouse 31100 FranceLAAS‐CNRS Université de Toulouse, CNRS, INSA Toulouse 31400 FranceCIBER “Fisiopatologia de la Obesidad y Nutrición”, Department of Biochemistry and Molecular Biomedicine University of Barcelona Madrid 28029 SpainCIBER “Fisiopatologia de la Obesidad y Nutrición”, Department of Biochemistry and Molecular Biomedicine University of Barcelona Madrid 28029 SpainRESTORE Research Center Université de Toulouse, INSERM 1301, CNRS 5070, EFS, ENVT Toulouse 31100 FranceRESTORE Research Center Université de Toulouse, INSERM 1301, CNRS 5070, EFS, ENVT Toulouse 31100 FranceLAAS‐CNRS Université de Toulouse, CNRS, INSA Toulouse 31400 FranceLAAS‐CNRS Université de Toulouse, CNRS, INSA Toulouse 31400 FranceService de Chirurgie plastique, reconstructrice et esthétique Centre Hospitalier Universitaire Rangueil Toulouse 31400 FranceFaculté de Médecine Université Côte d'Azur INSERM, CNRS, iBV Nice 06103 FranceRESTORE Research Center Université de Toulouse, INSERM 1301, CNRS 5070, EFS, ENVT Toulouse 31100 FranceRESTORE Research Center Université de Toulouse, INSERM 1301, CNRS 5070, EFS, ENVT Toulouse 31100 FranceRESTORE Research Center Université de Toulouse, INSERM 1301, CNRS 5070, EFS, ENVT Toulouse 31100 FranceFaculté de Médecine Université Côte d'Azur INSERM, CNRS, iBV Nice 06103 FranceRESTORE Research Center Université de Toulouse, INSERM 1301, CNRS 5070, EFS, ENVT Toulouse 31100 FranceLAAS‐CNRS Université de Toulouse, CNRS, INSA Toulouse 31400 FranceRESTORE Research Center Université de Toulouse, INSERM 1301, CNRS 5070, EFS, ENVT Toulouse 31100 FranceAbstract 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.https://doi.org/10.1002/advs.202301499adipose‐derived stroma/stem cells (ASC)beige and brown adipocytesguided‐assemblyhydrogelsmicrotissuesorganoid morphogenesis |
| spellingShingle | Mélanie Escudero Laurence Vaysse Gozde Eke 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 Scalable Generation of Pre‐Vascularized and Functional Human Beige Adipose Organoids Advanced Science adipose‐derived stroma/stem cells (ASC) beige and brown adipocytes guided‐assembly hydrogels microtissues organoid morphogenesis |
| title | Scalable Generation of Pre‐Vascularized and Functional Human Beige Adipose Organoids |
| title_full | Scalable Generation of Pre‐Vascularized and Functional Human Beige Adipose Organoids |
| title_fullStr | Scalable Generation of Pre‐Vascularized and Functional Human Beige Adipose Organoids |
| title_full_unstemmed | Scalable Generation of Pre‐Vascularized and Functional Human Beige Adipose Organoids |
| title_short | Scalable Generation of Pre‐Vascularized and Functional Human Beige Adipose Organoids |
| title_sort | scalable generation of pre vascularized and functional human beige adipose organoids |
| topic | adipose‐derived stroma/stem cells (ASC) beige and brown adipocytes guided‐assembly hydrogels microtissues organoid morphogenesis |
| url | https://doi.org/10.1002/advs.202301499 |
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