Engineering Vascularized and Immunized Organoids for Regenerative Medicine

Organoids provide powerful platforms for modeling human development and disease, but the lack of functional vascular and immune microenvironments remains a major barrier to their maturation and translational applications. I will present our strategies for engineering vascularized and immunized organoids from human pluripotent stem cells (hPSCs), with applications in regenerative medicine. By integrating multiple hPSC-derived cell types through multicellular assembly and biofabrication approaches, we generated vascularized and immune-competent cardiac, liver, and brain organoids. In cardiac organoids, integrative transcriptomic and epigenomic analyses revealed bidirectional interactions between cardiomyocytes and resident macrophages: the tissue environment reprogrammed macrophage states, while macrophage-derived paracrine factors promoted cardiomyocyte maturation and contractile function. We further developed vascularized and immune-competent brain organoids incorporating endothelial cells and microglia-like cells, which exhibited enhanced vascular formation, neuronal maturation, and neuro-immune-vascular interactions. Following transplantation into a stroke model, these organoids promoted cerebral blood flow recovery and functional improvement. Together, these studies highlight multicellular microenvironment engineering as a promising strategy to build more physiologically relevant organoids and advance their applications in regenerative medicine.

Dr Jie Na. Ph.D. is a professor at School of Basic Medical Sciences, Tsinghua University. She received her medical degree from Peking University, Ph.D. in Cell Biology from the University of Virginia, and completed postdoctoral training at the University of Cambridge, followed by a Stem Cell Career Development Fellowship from the UK Medical Research Council. She returned to China in 2010.

Her research focuses on stem cell and regenerative medicine, with interests in human pluripotent stem cell differentiation, organoid models of human development and disease, and cell-based therapies for vascular and tissue regeneration. She has led multiple NSFC and National Key R&D Program projects. Dr Jie Na has published more than 90 papers in leading journals, including Nature and Science, with over 5,000 citations.