title: Three-dimensional neural differentiation of embryonic stem cells with ACM induction in microfibrous matrices in bioreactors.
abstract: The clinical use of pluripotent stem cell (PSC)-derived neural cells requires an efficient differentiation process for mass production in a bioreactor. Toward this goal, neural differentiation of murine embryonic stem cells (ESCs) in three-dimensional (3D) polyethylene terephthalate microfibrous matrices was investigated in this study. To streamline the process and provide a platform for process integration, the neural differentiation of ESCs was induced with astrocyte-conditioned medium without the formation of embryoid bodies, starting from undifferentiated ESC aggregates expanded in a suspension bioreactor. The 3D neural differentiation was able to generate a complex neural network in the matrices. When compared to 2D differentiation, 3D differentiation in microfibrous matrices resulted in a higher percentage of nestin-positive cells (68% vs. 54%) and upregulated gene expressions of nestin, Nurr1, and tyrosine hydroxylase. High purity of neural differentiation in 3D microfibrous matrix was also demonstrated in a spinner bioreactor with 74% nestin + cells. This study demonstrated the feasibility of a scalable process based on 3D differentiation in microfibrous matrices for the production of ESC-derived neural cells.
authors: William G. Lowrie Dept. of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USA.
authors: Ning
authors: N
authors: Liu
authors: Anli
authors: A
authors: Ouyang
authors: Yan
authors: Y
authors: Li
authors: Shang-Tian
authors: ST
authors: Yang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D019149:Bioreactors; D002454:Cell Differentiation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry*; D053595:Embryonic Stem Cells / Q000166:cytology*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D051379:Mice; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D058953:Neural Stem Cells / Q000166:cytology*; D011093:Polyethylene Terephthalates / Q000737:chemistry
chemical_list: D017077:Culture Media, Conditioned; D011093:Polyethylene Terephthalates
keywords: astrocyte conditioned medium; bioreactor; embryonic stem cell; microfibrous matrix; neural differentiation; three-dimensional