Development of Muller cell-based 3D biomimetic model using bioprinting technology

초록

Muller cells are the principal glial cells for the maintenance of structural stability and metabolic homeostasis in the human retina. Although various in vitro experiments using two-dimensional (2D) monolayer cell cultures have been performed, the results provided only limited results because of the lack of 3D structural environment and different cellular morphology. We studied a Muller cell-based 3D biomimetic model for use in experiments on the in vivo-like functions of Muller cells within the sensory retina. Isolated primary Muller cells were bioprinted and a 3D-aligned architecture was induced, which aligned Muller cell structure in retinal tissue. The stereographic and functional characteristics of the biomimetic model were investigated and compared to those of the conventional 2D cultured group. The results showed the potential to generate Muller cell-based biomimetic models with characteristic morphological features such as endfeet, soma, and microvilli. Especially, the 3D Muller cell model under hyperglycemic conditions showed similar responses as observed in the in vivo diabetic model with retinal changes, whereas the conventional 2D cultured group showed different cytokine and growth factor secretions. These results show that our study is a first step toward providing advanced tools to investigate the in vivo function of Muller cells and to develop complete 3D models of the vertebrate retina.

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