A 3D Self‐Assembled In Vitro Model to Simulate Direct and Indirect Interactions between Adipocytes and Skeletal Muscle Cells

Abstract

The molecular mechanisms of the development and progression of diabetes and obesity involve complex interactions between adipocytes and skeletal muscle cells. Although 2D in‐vitro models are the gold standard for the mechanistic study of such behaviors, they do not recreate the complexity and dynamics of the interactions between the cell types involved. Alternatively, animal models are used but are expensive, difficult to visualize or analyze, are not completely representative of human physiology or genetic background, and have associated ethical considerations. 3D co‐culture systems can be complementary to these approaches. Here, using a newly developed 3D biofabrication method, adipocytes and myoblasts are positioned precisely either in direct physical contact or in close proximity such that the paracrine effects could be systematically studied. Suitable protocols for growth and differentiation of both cells in the co‐culture system is also developed. Cells show more restrained lipid and protein production in 3D systems compared to 2D ones and adipocytes show more lipolysis in indirect contact with myoblasts as response to drug treatment. These findings emphasize importance of physical contact between cells that have been overlooked in co‐culture systems using transwell inserts and can be used in studies for the development of anti‐obesity drugs.

Scaffolding Biomaterials for 3D Cultivated Meat: Prospects and Challenges

“…Several studies have reported the successful 2D coculture of myogenic and adipogenic cells from agriculturally relevant species, [ 429 , 430 , 431 , 432 ] while others have reported small‐scale 3D cultures using human or mouse cells. [ 120 , 428 , 433 ] In addition, the company Ants Innovate is developing a scaffolding system to support the growth of marbled meat containing muscle cells and fat. They have filed a patent on their biomaterial system, [ 434 ] and the founders have recently published an article using a cellulose sponge for organoid culture.…”

The Development of Biomimetic Aligned Skeletal Muscles in a Fully 3D Printed Microfluidic Device

“…This is particularly true given that skeletal myotubes are characterized by a unique topography represented in their aligned architecture that also imposes a great impact on their function [ 6 ]. More recently, 3D models of the skeletal muscles have also been developed through the employment of extracellular matrix (ECM) gels that could provide the mechanical cues for cells to expand and differentiate into myotubes [ 7 , 8 , 9 ]. However, it is difficult to recapitulate the dynamic conditions in these models including the recapitulation of blood flow and other factors such as mechanical stimuli [ 10 ].…”

Adipose and Muscle Cell Co-Culture System: A Novel In Vitro Tool to Mimic the In Vivo Cellular Environment

“…Recently, Chu et al (2016) [11] reported that porcine pre-adipocyte differentiation was inhibited in a C2C12 co-culture cells and that the expression levels of early differentiation marker genes in adipocytes were lower than those in mono-cultured adipocyte cells. Recently, Shahin-Shamsabadi [12] developed a 3D bio-fabrication method using adipocytes and myoblasts, that analyzed specifically either in direct physical contact or in close proximity such that the paracrine interaction between the cells. The physical contact between cells have been flouted in co-culture systems using transwell inserts and can be used in studies for the development of anti-obesity drugs.…”