Bioprinting of stem cell expansion lattices.

Abstract

Stem cells have great potential in regenerative medicine, with neural progenitor cells (NPCs) being developed as a therapy for many central nervous system diseases and injuries. However, one limitation to the clinical translation of stem cells is the resource-intensive, two-dimensional culture protocols required for biomanufacturing a clinically-relevant number of cells. This challenge can be overcome in an easy-to-produce and cost-effective 3D platform by bioprinting NPCs in a layered lattice structure. Here we demonstrate that alginate biopolymers are an ideal bioink for expansion lattices and do not require chemical modifications for effective NPC expansion. Alginate bioinks that are lightly crosslinked prior to printing can shield printed NPCs from potential mechanical damage caused by printing. NPCs within alginate expansion lattices remain in a stem-like state while undergoing a 2.5-fold expansion. Importantly, we demonstrate the ability to efficiently remove NPCs from printed lattices for future down-stream use as a cell-based therapy. These results demonstrate that 3D bioprinting of alginate expansion lattices is a viable and economical platform for NPC expansion that could be translated to clinical applications.