Oliver
Thomas Johnson

Creating a Xenografted Human Vascularized Chimeric Brain Model STEM

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Authors:

Oliver Thomas Johnson

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Cerebral blood vessels are essential for transporting nutrients throughout the brain and regulating the entry of materials into the brain through the Blood-Brain Barrier (BBB). Dysfunction of the brain's vascular system is linked to conditions such as stroke, vascular dementia, and Alzheimer's disease. Growing evidence shows significant differences between human and mouse vascular cells. For example, human vascular cells express higher levels of Alzheimer 's-associated genes. Therefore, it is urgent to develop human vascular models to better understand how the vascular system affects brain health and disease. An in vivo vascular model, in which human blood vessels are perfused and functionally integrated into the host's brain, has not yet been developed. To create these models, we will inject human Pluripotent Stem Cell (hPSC)-derived vascular progenitor cells into mice and allow the cells to grow and differentiate within the mouse brains. We will examine human vasculature maturation in host brains by harvesting, sectioning, and immunohistochemically staining the brains at different times post-cell injection. The staining will target markers for the main cell types needed for functional blood vessels and the Blood-Brain Barrier: endothelial cells, smooth muscle cells, pericytes, and astrocytes. Developing this chimeric vascularized brain model will provide a more physiologically relevant system for studying neurovascular contributions in healthy and diseased conditions, such as Alzheimer's disease and Vascular Dementia. Keywords: Neuroscience; Stem Cells; Blood Vessels; Alzheimer's Disease

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Purdue University / 2025

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Oliver Thomas Johnson