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A vascularized tumoroid model for human glioblastoma angiogenesis.

ABSTRACT: Glioblastoma (GBM) angiogenesis is critical for tumor growth and recurrence, making it a compelling therapeutic target. Here, a disease-relevant, vascularized tumoroid in vitro model with stem-like features and stromal surrounds is reported. The model is used to recapitulate how individual components of the GBM's complex brain microenvironment such as hypoxia, vasculature-related stromal cells and growth factors support GBM angiogenesis. It is scalable, tractable, cost-effective and can be used with biologically-derived or biomimetic matrices. Patient-derived primary GBM cells are found to closely participate in blood vessel formation in contrast to a GBM cell line containing differentiated cells. Exogenous growth factors amplify this effect under normoxia but not at hypoxia suggesting that a significant amount of growth factors is already being produced under hypoxic conditions. Under hypoxia, primary GBM cells strongly co-localize with umbilical vein endothelial cells to form sprouting vascular networks, which has been reported to occur in vivo. These findings demonstrate that our 3D tumoroid in vitro model exhibits biomimetic attributes that may permit its use as a preclinical model in studying microenvironment cues of tumor angiogenesis.

SUBMITTER: Tatla AS

PROVIDER: S-EPMC8486855 | biostudies-literature |

REPOSITORIES: biostudies-literature

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A human ACTH-secreting corticotroph tumoroid model: Novel Human ACTH-Secreting Tumor Cell in vitro Model.

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Vascularized human cortical organoids (vOrganoid) model cortical development in vivo

Project description:Modeling the processes of neuronal progenitor proliferation and differentiation to produce mature cortical neuron subtypes is essential for the study of human brain development and the search for potential cell therapies. We demonstrated a novel paradigm for the generation of vascularized organoids (vOrganoids) consisting of typical human cortical cell types and a vascular structure for over 200 days as a vascularized and functional brain organoid model. The observation of sEPSCs (spontaneous excitatory postsynaptic currents), sIPSCs (spontaneous inhibitory postsynaptic currents) and bidirectional electrical transmission indicated the presence of chemical and electrical synapses in vOrganoids. More importantly, single-cell RNA-sequencing analysis illustrated that vOrganoids exhibited robust neurogenesis and that cells of vOrganoids differentially expressed genes related to blood vessel morphogenesis. The transplantation of vOrganoids into the mouse S1 cortex resulted in the construction of functional human-mouse blood vessels in the grafts that promoted cell survival in the grafts. This vOrganoid culture method could not only serve as a model to study human cortical development and explore brain disease pathology but also provide potential prospects for new cell therapies for nervous system disorders and injury.

2020-06-04 | GSE131094 | GEO

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