Neural Differentiation of Spheroids Derived from Human Induced Pluripotent Stem Cells–Mesenchymal Stem Cells Coculture

Organoids, the condensed three-dimensional (3D) tissues emerged at the early stage of organogenesis, are a promising approach to regenerate functional and vascularized organ mimics. While incorporation of heterotypic cell types, such as human mesenchymal stem cells (hMSCs) and human induced pluripotent stem cells (hiPSCs)-derived neural progenitors aid neural organ development, the interactions of secreted factors during neurogenesis have not been well understood. The objective of this study is to investigate the impact of the composition and structure of 3D hybrid spheroids of hiPSCs and hMSCs on dorsal cortical differentiation and the secretion of extracellular matrices and trophic factors in vitro. The hybrid spheroids were formed at different hiPSC:hMSC ratios (100:0, 75:25, 50:50, 25:75, 0:100) using direct mixing or pre-hiPSC aggregation method, which generated dynamic spheroid structure. The cellular organization, proliferation, neural marker expression, and the secretion of extracellular matrix pr...