Rapid Generation of hPSC-Derived High Endothelial Venule Organoids with In Vivo Ectopic Lymphoid Tissue Capabilities

Researchers have developed a bioengineering approach using induced differentiation of human pluripotent stem cells to fabricate implantable lymphoid structures resembling lymph nodes (LNs) and tertiary lymphoid structures (TLS). This method aims to enhance the adaptive immune response, particularly for cancer immunotherapy. By combining primitive inducible endothelial cells with primary human LN fibroblastic reticular cells, they created high endothelial venule (HEV)-like structures capable of forming 3D organoids (HEVOs). When transplanted into immunodeficient mice, HEVOs successfully engrafted and formed lymphatic structures, attracting antigen-presenting cells and adoptively-transferred lymphocytes, thus demonstrating basic TLS capabilities. Moreover, HEVOs organized an immune response and facilitated anti-tumor activity by adoptively-transferred T lymphocytes. Overall, these experimental approaches offer a novel and scalable strategy for generating bioengineered TLS that can augment adaptive immune responses in vivo, presenting promising implications for therapeutic interventions.

This research highlights the significance of advanced human heart organoid systems in studying congenital heart defects under conditions resembling pregestational diabetes, offering insights into the underlying pathology and potential therapeutic avenues.