Fabricating 3-dimensional human brown adipose microtissues for transplantation studies

Wang, Ou; Han, Li; Lin, Haishuang; Tian, Mingmei; Zhang, Shuyang; Duan, Bin; Chung, Soonkyu; Zhang, Chi; Lian, Xiaojun; Wang, Yong; Lei, Yuguo

doi:10.1016/j.bioactmat.2022.10.022

Cited by 4 publications

(35 citation statements)

References 105 publications

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“…Furthermore, engineered 3D human BA microtissues based on brown adipose precursor cells have been developed. 30 Using this technology is expected to achieve excellent therapeutic results in fine areas such as the face and mouth. Besides determining the optimal therapeutic window for LoS in BAT, transplanting BAT at different LoS stages to determine the treatment time will be a crucial research direction in the future.…”

Section: Discussionmentioning

confidence: 99%

“…The use of functional brown fat cell‐assisted transplantation can also further optimize ordinary fat transplantation therapy. Furthermore, engineered 3D human BA microtissues based on brown adipose precursor cells have been developed 30 . Using this technology is expected to achieve excellent therapeutic results in fine areas such as the face and mouth.…”

Section: Discussionmentioning

confidence: 99%

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Brown adipose tissue transplantation improves skin fibrosis in localized scleroderma

Zhang,

Liang,

Zhang

et al. 2023

The FASEB Journal

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Adipose tissue transplantation shows great therapeutic potential in reversing localized scleroderma‐associated skin fibrosis. Brown adipose tissue (BAT) can specifically secrete various cytokines against fibrosis, but its therapeutic potential in improving skin fibrosis has not yet been demonstrated. In this study, we have demonstrated the superior therapeutic efficacy of BAT transplantation for sclerotic skin by transplanting two distinct types of adipose tissue. In comparison to the white adipose tissue (WAT) group, mice treated with BAT transplantation exhibited a significant reduction in dermal thickness. BAT transplantation effectively reverses skin sclerosis through mechanisms involving inflammation reduction, promotion of angiogenesis, inhibition of myofibroblast accumulation, and collagen deposition. This therapeutic effect can be attributed to its unique paracrine effects. Furthermore, transcriptome sequencing (RNA‐Seq) revealed upregulation of pathways associated with lipogenesis and fatty acid metabolism in BAT while downregulating pathways are related to transforming growth factor β(TGF‐β), epithelial–mesenchymal transition (EMT), and inflammatory response. These findings suggest that BAT transplantation holds great promise as a novel approach for localized scleroderma treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Brown adipose tissue transplantation improves skin fibrosis in localized scleroderma

Zhang,

Liang,

Zhang

et al. 2023

The FASEB Journal

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“…Beige adipocytes emerge sporadically in WATs postnatally in response to cold exposure or other certain stimuli 24 . The multilocular structure of adipocytes in BrAOs and BeAOs is usually characterized by phase contrast imaging 34 , 35 , scanning and transmission electron microscopy imaging 35 , H&E staining 36 , Oil Red O 37 , LipidTox Green 35 , and BODIPY staining 38 , and perilipin immunostaining 39 . Moreover, dense mitochondria with high UCP1 expression are usually characterized by immunostaining 35 , 36 .…”

Section: Adipose Organoid An Emerging Tool To Combat Omdsmentioning

confidence: 99%

“…The multilocular structure of adipocytes in BrAOs and BeAOs is usually characterized by phase contrast imaging 34 , 35 , scanning and transmission electron microscopy imaging 35 , H&E staining 36 , Oil Red O 37 , LipidTox Green 35 , and BODIPY staining 38 , and perilipin immunostaining 39 . Moreover, dense mitochondria with high UCP1 expression are usually characterized by immunostaining 35 , 36 . They also express thermogenic markers such as UCP1, DIO2, CIDEA, PPARGC1A, and PRDM16 24 .…”

Section: Adipose Organoid An Emerging Tool To Combat Omdsmentioning

confidence: 99%

“…Besides, the Seahorse bioanalyzer is often used to assess energy extracellular acidification rates for anaerobic glycolysis and OCR for aerobic mitochondrial respiration 35 . BrAOs and BeAOs also secret batokines which improve insulin-resistance 39 and endogenous adipokine secretion 36 . Therefore, the functions of non-shivering thermogenesis and metabolic healthy secretion enable BrAOs and BeAOs to treat OMDs after transplantation 7 , 21 .…”

Section: Adipose Organoid An Emerging Tool To Combat Omdsmentioning

confidence: 99%

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Unleashing the potential of adipose organoids: A revolutionary approach to combat obesity-related metabolic diseases

Liu,

Yang,

Yan

et al. 2024

Theranostics

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Obesity-related metabolic diseases, including obesity, diabetes, hyperlipidemia, and non-alcoholic fatty liver diseases pose a significant threat to health. However, comprehensive pathogenesis exploration and effective therapy development are impeded by the limited availability of human models. Notably, advances in organoid technology enable the generation of adipose organoids that recapitulate structures and functions of native human adipose tissues to investigate mechanisms and develop corresponding treatments for obesity-related metabolic diseases. Here, we review the general principles, sources, and three-dimensional techniques for engineering adipose organoids, along with strategies to promote maturation. We also outline the application of white adipose organoids, primarily for disease modeling and drug screening, and highlight the therapeutic potential of thermogenic beige and brown adipose organoids in promoting weight loss and glucose and lipid metabolic homeostasis. We also discuss the challenges and prospects in the establishment and bench-to-bedside of adipose organoids, as well as their potential applications.

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Transplantation of beige adipose organoids fabricated using adipose acellular matrix hydrogel improves metabolic dysfunction in high‐fat diet‐induced obesity and type 2 diabetes mice

Quan,

Li,

Cai

et al. 2024

Journal Cellular Physiology

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Transplantation of brown adipose tissue (BAT) is a promising approach for treating obesity and metabolic disorders. However, obtaining sufficient amounts of functional BAT or brown adipocytes for transplantation remains a major challenge. In this study, we developed a hydrogel that combining adipose acellular matrix (AAM) and GelMA and HAMA that can be adjusted for stiffness by modulating the duration of light‐crosslinking. We used human white adipose tissue‐derived microvascular fragments to create beige adipose organoids (BAO) that were encapsulated in either a soft or stiff AAM hydrogel. We found that BAOs cultivated in AAM hydrogels with high stiffness demonstrated increased metabolic activity and upregulation of thermogenesis‐related genes. When transplanted into obese and type 2 diabetes mice, the HFD + BAO group showed sustained improvements in metabolic rate, resulting in significant weight loss and decreased blood glucose levels. Furthermore, the mice showed a marked reduction in nonalcoholic liver steatosis, indicating improved liver function. In contrast, transplantation of 2D‐cultured beige adipocytes failed to produce these beneficial effects. Our findings demonstrate the feasibility of fabricating beige adipose organoids in vitro and administering them by injection, which may represent a promising therapeutic approach for obesity and diabetes.

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Fabricating 3-dimensional human brown adipose microtissues for transplantation studies

Cited by 4 publications

References 105 publications

Brown adipose tissue transplantation improves skin fibrosis in localized scleroderma

Brown adipose tissue transplantation improves skin fibrosis in localized scleroderma

Unleashing the potential of adipose organoids: A revolutionary approach to combat obesity-related metabolic diseases

Transplantation of beige adipose organoids fabricated using adipose acellular matrix hydrogel improves metabolic dysfunction in high‐fat diet‐induced obesity and type 2 diabetes mice

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