Project description:To investigate the cell-cell interactions among the transplanted vascularized organoids, we utilized a Slide-seq-based spatial transcriptomics platform to unbiasedly map the spatial distribution of ligand-receptor pairs.
Project description:Organotypic mesenchyme and endothelium are pivotal during organ development. To generate these context-specific cell types, we established human pluripotent stem cell (hPSC)-derived meso-endoderm spheroids and vascularized primitive gut tube organoids and benchmarked this process via single-cell RNA-seq.
Project description:Organoids have been widely used as unique models of human brain development and disorders. However, the lack of vasculatures in brain orgnoids limits their application in the study of brain vasculature development and diseases. Here, we described to the generation of vascularized brain organoids (VBOrs) with different brain regions from human embryonic stem cells. The goals of this study are to analyze the cell populations of the new model of vasularized brain organoids cultured from human embryonic stem cells (H9). We found that VBOrs contain variant brain cells inculding neural progenitors, neuronal cells, astrocytes, sparse endothelial cells, and pericytes. The new model of VBOrs should be valuable for addressing questions between brain vasculatures and neural cells.
Project description:Human induced pluripotent stem cell-derived kidney organoids have potential for disease modelling and regenerative medicine purposes. However, they lack a functional vasculature and remain immature in in vitro culture. Here, we transplanted kidney organoids at day 7+12 of differentiation in the coelomic cavity of chicken embryos and then compared them to their respective untransplanted controls at d7+13 and d7+20 using scRNAseq and imaging modalities. We demonstrate vascularization and enhanced maturation of transplanted kidney organoids.
Project description:Pharmacokinetic/pharmacodynamic (PK/PD) studies are an essential component of pre-clinical drug discovery. Current best approaches for PK/PD studies, including the analysis of novel kidney disease targeting therapeutic agents, are limited to animal models with unclear translatability to the human condition. To address this challenge, we developed a novel approach for PK/PD studies using transplanted human kidney organoids. We performed PK studies with GFB-887, an investigational new drug now in Phase 2 trials. Orally dosed GFB-887 to athymic rats that had undergone organoid transplantation resulted in measurable drug exposure in human transplanted organoids. Importantly, we established the efficacy of orally dosed GFB-887 in PD studies, where quantitative analysis showed significant protection of kidney filter cells in human organoids and endogenous rat host kidneys. This widely applicable approach demonstrates, for the first time, feasibility of using transplanted human organoids in PK/PD studies, empowering organoids to revolutionize drug discovery.