Enhanced contractile force generation by artificial skeletal muscle tissues using IGF-I gene-engineered myoblast cells(CELL AND TISSUE ENGINEERING)

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概要

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• The aim of this study was to investigate whether insulin-like growth factor (IGF)-I gene delivery to myoblast cells promotes the contractile force generated by hydrogel-based tissue-engineered skeletal muscles in vitro. Two retroviral vectors allowing doxycycline (Dox)-inducible expression of the IGF-I gene were transduced into mouse myoblast C2C12 cells to evaluate the effects of IGF-I gene expression on these cells. IGF-I gene expression stimulated the proliferation of C2C12 cells, and a significant increase in the growth rate was observed for IGF-I-transduced C2C12 cells with Dox addition, designated C2C12/IGF (Dox+) cells. Quantitative morphometric analyses showed that the myotubes induced from C2C12/IGF (Dox+) cells had a larger area and a greater width than control myotubes induced from normal C2C12 cells. Artificial skeletal muscle tissues were prepared from the respective cells using hydrogels composed of type I collagen and Matrigel. Western blot analyses revealed that the C2C12/IGF (Dox+) tissue constructs showed activation of a skeletal muscle hypertrophy marker (Akt) and enhanced expression of muscle-specific markers (myogenin, myosin heavy chain and tropomyosin). Moreover, the creatine kinase activity was increased in the C2C12/IGF (Dox+) tissue constructs. The C2C12/IGF (Dox+) tissue constructs contracted in response to electrical pulses, and generated a significantly higher physical force than the control C2C12 tissue constructs. These findings indicate that IGF-I gene transfer has the potential to yield functional skeletal muscle substitutes that are capable of in vivo restoration of the load-bearing function of injured muscle or acting as in vitro electrically-controlled bio-actuators.

著者

• Nagamori Eiji

  Toyota Central R & D Laboratories Inc.

• Kamihira Masamichi

  Graduate School of Systems Life Sciences, Kyushu University

• Kamihira M

  Department Of Biotechnology School Of Engineering Nagoya University

• Kamihira Masamichi

  Nagoya University:(present Office)kyushu University

• Kamihira Masamichi

  名古屋大学 工学研究科生物機能工学

• Kamihira Masamichi

  Department Of Biotechnology Graduate School Of Engineering Nagoya University

• Nagamori Eiji

  Department Of Biotechnology School Of Engineering Nagoya University

• Nagamori Eiji

  Toyota Central R & D Labs. Inc.

• Nagamori E

  Osaka Univ. Osaka Jpn

• Nagamori Eiji

  Biotechnology Laboratory Toyota Central R&d Labs Inc.

• Kawabe Yoshinori

  Department Of Chemical Engineering Faculty Of Engineering Kyushu University

• Kawabe Yoshinori

  九州大学 大学院システム生命科学府

• Kawabe Yoshinori

  九州大学 工学研究院化学工学

• Kamihira Masamichi

  Department Of Chemical Engineering Faculty Of Engineering Nagoya University

• Ito Akira

  Department Of Chemical Engineering Faculty Of Engineering Kyushu University

• Ito Akira

  Department Of Biochemistry And Molecular Biology School Of Pharmacy Tokyo University Of Pharmacy And

• Sato Masanori

  Department Of Earth And Environmental Sciences Faculty Of Science Kagoshima University

• Sato Masanori

  Department Of Chemical Engineering Faculty Of Engineering Kyushu University

• Sato Masanori

  Department Of Applied Physics Tokyo University Of Agriculture And Technology

• Kawabe Yoshinori

  Department Of Biotechnology Graduate School Of Engineering Nagoya University

• Ito Akira

  Department of Chemical Engineering, Faculty of Engineering, Kyushu University

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