Smooth muscle-like tissue constructs with circumferentially oriented cells formed by the cell fiber technology.
The proper functioning of many organs and tissues containing smooth muscles greatly depends on the intricate organization of the smooth muscle cells oriented in appropriate directions. Consequently controlling the cellular orientation in three-dimensional (3D) cellular constructs is an important issue in engineering tissues of smooth muscles. However, the ability to precisely control the cellular orientation at the microscale cannot be achieved by various commonly used 3D tissue engineering building blocks such as spheroids. This paper presents the formation of coiled spring-shaped 3D cellular constructs containing circumferentially oriented smooth muscle-like cells differentiated from dedifferentiated fat (DFAT) cells. By using the cell fiber technology, DFAT cells suspended in a mixture of extracellular proteins possessing an optimized stiffness were encapsulated in the core region of alginate shell microfibers and uniformly aligned to the longitudinal direction. Upon differentiation induction to the smooth muscle lineage, DFAT cell fibers self-assembled to coiled spring structures where the cells became circumferentially oriented. By changing the initial core-shell microfiber diameter, we demonstrated that the spring pitch and diameter could be controlled. 21 days after differentiation induction, the cell fibers contained high percentages of ASMA-positive and calponin-positive cells. Our technology to create these smooth muscle-like spring constructs enabled precise control of cellular alignment and orientation in 3D. These constructs can further serve as tissue engineering building blocks for larger organs and cellular implants used in clinical treatments.
Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.
Amy Y
AY
Hsiao
Institute of Industrial Science, The University of Tokyo, Tokyo, Japan; ERATO Takeuchi Biohybrid Innovation Project, Japan Science and Technology Agency, Tokyo, Japan.
Teru
T
Okitsu
Institute of Industrial Science, The University of Tokyo, Tokyo, Japan; ERATO Takeuchi Biohybrid Innovation Project, Japan Science and Technology Agency, Tokyo, Japan.
Hiroaki
H
Onoe
Institute of Industrial Science, The University of Tokyo, Tokyo, Japan; ERATO Takeuchi Biohybrid Innovation Project, Japan Science and Technology Agency, Tokyo, Japan.
Mahiro
M
Kiyosawa
Faculty of Teacher Education, Shumei University, Chiba, Japan.
Hiroki
H
Teramae
Institute of Industrial Science, The University of Tokyo, Tokyo, Japan; ERATO Takeuchi Biohybrid Innovation Project, Japan Science and Technology Agency, Tokyo, Japan.
Shintaroh
S
Iwanaga
Department of Functional Morphology, Division of Cell Regeneration and Transplantation, Nihon University School of Medicine, Tokyo, Japan.
Tomohiko
T
Kazama
Department of Functional Morphology, Division of Cell Regeneration and Transplantation, Nihon University School of Medicine, Tokyo, Japan.
Taro
T
Matsumoto
Institute of Industrial Science, The University of Tokyo, Tokyo, Japan; ERATO Takeuchi Biohybrid Innovation Project, Japan Science and Technology Agency, Tokyo, Japan.
Shoji
S
Takeuchi
D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000464:Alginates / Q000737:chemistry; D000818:Animals; D001323:Autoantibodies / Q000737:chemistry; D015415:Biomarkers / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D018929:Cell Culture Techniques / Q000295:instrumentation*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004867:Equipment Design; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry; D056656:Lab-On-A-Chip Devices; D008840:Microfilament Proteins / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism; D011817:Rabbits; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*; D054457:Tissue Scaffolds; D000096985:Calponins
D000464:Alginates; D001323:Autoantibodies; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D020100:Hydrogels; D008840:Microfilament Proteins; D000096985:Calponins; C051931:myasthenia gravis anti-skeletal muscle antibody