Generation of functional fat organoid from rat superficial fascia

Abstract

The organoid is a 3D cell architecture formed by self-organized tissues or cells in vitro with similar cell types, histological structures, and biological functions of the native organ. Depending on the unique organ structures and cell types, producing organoids requires individualized design and is still challenging. Organoids of some tissues, including adipose tissue, remain to generate to be more faithful to their original organ in structure and function. We previously established a new model of the origin of adipose cells originating from non-adipose fascia tissue. Here, we investigated superficial fascia fragments in 3D hydrogel and found they were able to transform into relatively large adipocyte aggregates containing mature unilocular adipocytes, which were virtually “fat organoids”. Such fascia-originated fat organoids had a typical structure of adipose tissues and possessed the principal function of adipose cells in the synthesis, storage, hydrolysis of triglycerides and adipokines secretion. Producing fat organoids from superficial fascia can provide a new approach for adipocyte research and strongly evidences that both adipose tissues and cells originate from fascia. Our findings give insights into metabolic regulation by the crosstalk between different organs and tissues and provide new knowledge for investigating novel treatments for obesity, diabetes and other metabolic diseases. Abbreviations : 3D: three dimensional; ASC: adipose-derived stromal cells; C/EBP: CCAAT-enhancer-binding protein; EdU: 5-ethynyl-2-deoxyuridine; FABP4: fatty acid-binding protein 4; FAS: fatty acid synthase; FSCs: fascia-derived stromal cells; Plin1: perilipin-1; Plin2: perilipin-2; PPARγ: peroxisome proliferator-activated receptor γ; WAT: white adipose tissue

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

“…In practice, the term 'adipose organoid' has often been used interchangeably with other terms, such as 'adipose spheroid' 42 , 'adipocyte aggregate' 43 , 'fat organoid' 44 , 'adipose tissue' 38 , 45 , and 'adipose microtissue' 36 . Considering the structures and functions they exhibited, we discuss them uniformly in the term 'adipose organoid' in the following section.…”

“…Through embedding fragments of the rat superficial fascia (1-3 mm 3 ) in fibrin hydrogels, seeding liquified human lipoaspirates into silk scaffolds, or sandwiching human primary WAT fragments (0.5-1 mm) between SVF-derived adipose sheets, WATs were reconstructed to maintain viable and functional for longer time (over 3 months) 28 , 79 than primary explants. These WAOs exhibited unilocular structure and functions in lipogenesis 28 , 44 , lipolysis 28 , 44 , 79 , and adipokine secretion 28 , 44 , 79 . To generate BeAOs from micro-WATs, β-adrenergic agonists, cAMP activators, and angiogenic compounds are usually supplemented.…”

Transplantation of in vitro prefabricated adipose organoids attenuates skin fibrosis by restoring subcutaneous fat and inducing dermal adipogenesis

“…[10][11][12] Recent studies have shown that adipose organoids (ad-organoids) have high viability and purity, and mimic the biological activity of adipose tissue under physiological regulation. [13][14][15] Transplanted ad-organoids embedded in hydrogel show promising long-term survival without complications. 16,17 In addition, the miniaturized ad-organoid allows a higher ratio of blood oxygen exchange, and transplants can enter the intradermal layer precisely.…”

“…An organoid is a miniaturized and simplified version of an organ produced in vitro in three dimensions that has realistic microanatomy and sustains the original function 10–12 . Recent studies have shown that adipose organoids (ad‐organoids) have high viability and purity, and mimic the biological activity of adipose tissue under physiological regulation 13–15 . Transplanted ad‐organoids embedded in hydrogel show promising long‐term survival without complications 16,17 .…”

Gellan Gum Is a Suitable Biomaterial for Manual and Bioprinted Setup of Long-Term Stable, Functional 3D-Adipose Tissue Models

“…Only limited studies were found using a human 3D adipose tissue model as spheroids or microfluidic system [ 33 , 34 , 35 , 36 , 37 ] to mimic the native situation in more detail. Despite all studies creating important data for understanding mechanisms in adipose tissue, they rely on not fully matured ASCs, xenogenic cells, or have only been evaluated over a short period.…”