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:We recently established a hPSC-derived 3D organoid system to mimic the vascularization process during lung differentiation. To further mature the organoid, we embedded them into the mouse kidney capsule for three months and observed the accumulation of fluid within the growing organoids. Therefore, we aim to understand if there are any proteins related to lung function are being secreted in this case.
Project description:Here, we demonstrate a generalized method for organ bud formation from diverse tissues by combining pluripotent stem cell-derived tissue-specific progenitors or relevant tissue samples with endothelial cells and mesenchymal stem cells (MSCs). The MSCs initiated condensation within these heterotypic cell mixtures, which was dependent upon substrate matrix stiffness. Defining optimal mechanical properties promoted formation of 3D, transplantable organ buds from tissues including kidney, pancreas, intestine, heart, lung, and brain. Transplanted pancreatic and renal buds were rapidly vascularized and self-organized into functional, tissue-specific structures. These findings provide a general platform for harnessing mechanical properties to generate vascularized, complex organ buds with broad applications for regenerative medicine. Gene expression profiles of development-related gene expression in kidney bud transplants and murine kidneys.
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:The vasculature is essential for tissue function and pathology. Spheroid co-cultures of endothelial and mesenchymal stem/stromal cells (MSCs) form consistent structures, but the vascular components are short-lived. iPSC-derived vascular organoids can establish complex vasculature but often have cell heterogeneous variable maturation and low reproducibility. We presents consistently-formed, free-floating, long-term Vascularized Mesenchymal Organoids (VMOs), formed by co-culturing human umbilical vein endothelial cells (HUVECs) and MSCs in a pre-gelled minimal Matrigel scaffold. We studied, MSC heterogeneity, vascular biology and system dynamics.
Project description:The vasculature is essential for tissue function and pathology. Spheroid co-cultures of endothelial and mesenchymal stem/stromal cells (MSCs) form consistent structures, but the vascular components are short-lived. iPSC-derived vascular organoids can establish complex vasculature but often have cell heterogeneous variable maturation and low reproducibility. We presents consistently-formed, free-floating, long-term Vascularized Mesenchymal Organoids (VMOs), formed by co-culturing human umbilical vein endothelial cells (HUVECs) and MSCs in a pre-gelled minimal Matrigel scaffold. We studied organoid dynamics over 60 days culture time and used spheroids cultured for 14 days as control.