Biofabrication. 2017 Mar 13. doi: 10.1088/1758-5090/aa663b. [Epub ahead of print]

Three-dimensional tissues using human pluripotent stem cell spheroids as biofabrication building blocks.

Lin H¹, Li Q², Lei Y³.

Abstract

A recently emerged approach for tissue engineering is to biofabricate tissues using cellular spheroids as building blocks. Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), can be cultured to generate large numbers of cells and presumably be differentiated into all the cell types of human body in vitro, thus are ideal cell source for biofabrication. We previously developed a hydrogel-based cell culture system that can economically produce large numbers of hPSC spheroids. With hPSCs and this culture system, there are two potential methods to biofabricate a desired tissue. In Method 1, hPSC spheroids are first utilized to biofabricate a hPSC tissue that is subsequently differentiated into the desired tissue. In Method 2, hPSC spheroids are first converted into tissue spheroids in the hydrogel-based culture system and the tissue spheroids are then utilized to biofabricate the desired tissue. In this paper, we systematically measured the fusion rates of hPSC spheroids without and with differentiation toward cortical and midbrain dopaminergic neurons and found spheroids' fusion rates dropped sharply as differentiation progressed. We found Method 1 was appropriated for biofabricating neural tissues.