Tri‐culture of spatially organizing human skeletal muscle cells, endothelial cells, and fibroblasts enhances contractile force and vascular perfusion of skeletal muscle tissues
Name
The FASEB Journal - 2022 - Kim - Tri‐culture of spatially organizing human skeletal muscle cells endothelial cells and.pdf
Description
Published version
Size
4.9 MB
Format
Adobe PDF
Checksum (MD5)
38bbc1c07f5eeb0074a19bbb890d3417
Author(s)
Kim, Hyeonyu
Osaki, Tatsuya
Kamm, Roger D
Asada, H Harry
Date Issued
August 2022
Journal
The FASEB Journal
Publisher
Wiley
Citation
Kim, Hyeonyu, Osaki, Tatsuya, Kamm, Roger D and Asada, H Harry. 2022. "Tri‐culture of spatially organizing human skeletal muscle cells, endothelial cells, and fibroblasts enhances contractile force and vascular perfusion of skeletal muscle tissues." The FASEB Journal, 36 (8).
Version
Final published version
Abstract
Constructing engineered human skeletal muscle tissues that resemble the function and microstructure of human skeletal muscles is key to utilizing them in a variety of applications such as drug development, disease modeling, regenerative medicine, and engineering biological machines. However, current in vitro skeletal muscle tissues are far inferior to native muscles in terms of contractile function and lack essential cues for muscle functions, particularly heterotypic cell-cell interactions between myoblasts, endothelial cells, and fibroblasts. Here, we develop an engineered muscle tissue with a coaxial three-layered tubular structure composed of an inner endothelial cell layer, an endomysium-like layer with fibroblasts in the middle, and an outer skeletal muscle cell layer, similar to the architecture of native skeletal muscles. Engineered skeletal muscle tissues with three spatially organized cell types produced thicker myotubes and lowered Young's modulus through extracellular matrix remodeling, resulting in 43% stronger contractile force. Furthermore, we demonstrated that fibroblasts localized in the endomysium layer induced angiogenic sprouting of endothelial cells into the muscle layer more effectively than fibroblasts homogeneously distributed in the muscle layer. This layered tri-culture system enables a structured spatial configuration of the three main cell types of skeletal muscle and promotes desired paracrine signaling, resulting in improved angiogenesis and increased contractile force. This research offers new insights to efficiently obtain new human skeletal muscle models, transplantable tissues, and actuators for biological machines.
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution NonCommercial License 4.0
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1096/fj.202200500r
