(193f) Heterotypic Cell-Cell Interactions of Human Induced Pluripotent Stem Cells and Human Mesenchymal Stem Cells for Neural Differentiation

Organ buds, the condensed 3-D tissues emerged at the early stage of organogenesis, are a promising transplantation entity to regenerate functional and vascularized organs. However, complex heterotypic interactions of different cell types, such as human mesenchymal stem cells (hMSCs) and human induced pluripotent stem cell (hiPSC) derived neural progenitors, and their secretory activities during neurogenesis have not been well understood. The objective of this study is to investigate the impact of the composition and structure of 3-D hybrid spheroids of hiPSCs and hMSCs on neural 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 and pre-hiPSC aggregation method, which generated dynamic spheroid structure. The cellular organization, proliferation, neural marker expression, the secretion of extracellular matrix proteins and the cytokines were characterized. The incorporation of MSCs upregulated the neural marker expression, matrix remodeling proteins and the secretion of transforming growth factor (TGF)-β1 and prostaglandin E2. This study indicates that the composition and structure of hiPSC-MSC spheroids differentially influence neural differentiation and trophic factor and matrix secretion due to the modulation of heterotypic cell-cell interactions.