Recent progress in induced pluripotent stem (iPS) cell technology will open up a new stage in the field of regenerative medicine. Researchers believe that iPS cells can become a powerful tool to achieve effective cell-based therapies. This technology is also expected to allow us to create human cell-based physiological tissue models for drug discovery. To make a success of these challenges, however, tissue engineering technology is also necessary. In particular, a great deal of tissue engineering research has focused on technology for the creation of complex tissue constructs composed of multiple cell types.
In this vein, Hironobu Takahashi et al. from Tokyo Women’s Medical University have reported a unique method for structural organization of engineered tissue construct. A tissue-like cell assembly, called a “cell sheet”, is a useful tool to create 3D tissue constructs, since multiple cell sheets can be tightly layered each other.
Using the newly developed micro-fabricated cell culture substrate, aligned myoblasts, precursor muscle cells can be manipulated as a single myoblast sheet and their multiple myoblast sheets can be layered while maintaining the aligned orientation. In this study, they succeeded in the creation of biomimetic cellular networks composed of neurons and endothelial cells by sandwiching these cells between multiple anisotropic cell sheets.
Uniquely, this simple procedure provided neurons and endothelial cells with a microenvironment to self-organize anisotropic networks like in native muscle tissue. Well-aligned muscle cell orientation is known to be a key factor for producing mechanical functions in native skeletal muscle. Furthermore, nerves and vessels are also essential to generate its biomimetic tissue functions.
Whereas the control of cellular behaviors at the micro-scale level is difficult, this newly developed tissue engineering method allows us to create not only 3D oriented muscle tissue but also micro-structures of neurons and endothelial cells within the construct. This simple technique for organizing complex structures is believed to be useful for next-generation tissue engineering required for future advances in regenerative medicine and the development of in vitro tissue models.