Three-dimensional co-culture of C2C12/PC12 cells improves skeletal muscle tissue formation and function

Serge Ostrovidov, Samad Ahadian, Javier Ramon-Azcon, Vahid Hosseini, Toshinori Fujie, S. Prakash Parthiban, Hitoshi Shiku, Tomokazu Matsue, Hirokazu Kaji, Murugan Ramalingam, Hojae Bae, Ali Khademhosseini*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)


Engineered muscle tissues demonstrate properties far from native muscle tissue. Therefore, fabrication of muscle tissues with enhanced functionalities is required to enable their use in various applications. To improve the formation of mature muscle tissues with higher functionalities, we co-cultured C2C12 myoblasts and PC12 neural cells. While alignment of the myoblasts was obtained by culturing the cells in micropatterned methacrylated gelatin (GelMA) hydrogels, we studied the effects of the neural cells (PC12) on the formation and maturation of muscle tissues. Myoblasts cultured in the presence of neural cells showed improved differentiation, with enhanced myotube formation. Myotube alignment, length and coverage area were increased. In addition, the mRNA expression of muscle differentiation markers (Myf-5, myogenin, Mefc2, MLP), muscle maturation markers (MHC-IId/x, MHC-IIa, MHC-IIb, MHC-pn, α-actinin, sarcomeric actinin) and the neuromuscular markers (AChE, AChR-ε) were also upregulated. All these observations were amplified after further muscle tissue maturation under electrical stimulation. Our data suggest a synergistic effect on the C2C12 differentiation induced by PC12 cells, which could be useful for creating improved muscle tissue.

Original languageEnglish
Pages (from-to)582-595
Number of pages14
JournalJournal of Tissue Engineering and Regenerative Medicine
Issue number2
Publication statusPublished - 2017 Feb 1


  • C2C12
  • hydrogel
  • methacrylated gelatin
  • muscle
  • myogenesis
  • myotubes
  • PC12

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering


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