浅筋膜起源的脂肪类器官构建及其功能应用研究

类器官是原代或永生化组织细胞离体三维培养形成的细胞集聚体，具有与源组织相似的结构和功能。类器官的构建颇具个性化和挑战性，目前尚有多种组织包括脂肪类器官尚未构建成功。我们曾报道脂肪可起源于浅筋膜的新模型，提出浅筋膜脂肪细胞是一种功能异质性的新的脂肪细胞类型。我们在三维培养体系已将浅筋膜细胞分化为只含单一大脂滴的成熟脂肪细胞，意识到如此集聚成簇的脂肪细胞其实就是脂肪类器官雏形。本项目拟构建和表征大鼠浅筋膜源性脂肪类器官，模拟体内生理环境形成具有典型脂肪组织细胞形态和甘油三酯合成储存与脂肪分解功能，为脂肪可能起源于浅筋膜的学说提供有力证据，探索浅筋膜未曾被认知的功能，拓宽对脂肪起源的认识并有助于探索新的肥胖控制策略。浅筋膜在体内广泛存在、容易取材再生而不明显影响身体功能，尝试构建人浅筋膜源性的脂肪类器官，有用于再生医学和塑形外科组织填充修复美容的价值，也有制备高效的脂肪类器官生物反应器的前景。

Organoids are large three-dimensional cellular aggregates that can be derived from various cell sources such as primary tissue and cells, cell lines, embryonic, adult and pluripotent stem cells, and closely resemble their original organ cell types, structures and functions. The production of self-organizing 3D organoids of multiple organs has received considerable attention over the last 10 years. However, Dependent on the characteristics of the organ structure and cell types, the production of 3D organoids requires individualized designing and is still challenging. Organoids of some certain organs and tissues, including adipose tissue, remain to be generated with more faithful tissue like structures and functions. We have previously established a novel model of the origin of adipose cells, originated from nonadipose fascia tissue. Fascia is enriched with abundant preadipocytes that are capable of spontaneous adipogenic differentiation and are highly active in vivo. Adipocytes arisen from fascial preadipocytes gradually gather to form a thin layer of adipose cells and then primitive adipose lobules. Our preliminary observations show that fascia fragments and fascial preadipocytes in the 3D hydrogel culture were able to transform relatively large adipocyte aggregates, which is virtually a so called organoid of adipose tissue. In this project, we select the superficial fascia of rat limbs as experimental sample, because the fascia in rat, different from the fascia in human, contains a less amount of mature adipocytes and is easily dissected from adjacent tissues. We aim to establish an adipose-tissue organoid derived from nonadipose superficial fascia in an optimized 3D culture system. Such fascia-originated fat organoid is provided with typical structure of adipose tissue and cells, and process the principal function of adipose cells on the synthesis, storage, and hydrolysis of triglycerides. Fat organoid originated from fascia provides a new approach for the field of adipocyte research, and shows broad perspective of its application in regenerative medicine and plastic surgery, and also may be used for building fat organoid based bioreactor when combined with microfluidic technique. Most importantly, the generation of fascia-derived fat organoid could provide strong evidence showing that both adipose tissue and cells can be originated from the fascia, a nonadipose tissue. This project could reveal that nonadipose fascia participates in the neogenesis or formation of adipose cells and hence the regulation of adipose metabolism, novel functions of the fascia that have not yet been unrecognized by classical histoanatomy. This study may highlight the insight on metabolic regulation by the crosstalk between multiple different organs and tissues, and provide new knowledge for investigating novel anti-obesity strategy.