Generation of human vascularized brain organoids

TLDR

The study aimed to vascularize brain organoids using a patient’s own endothelial cells. Patient‑derived iPSCs were differentiated into brain organoids and endothelial cells, co‑cultured in Matrigel on day 34, then cultured in vitro for 3–5 weeks or transplanted into immunodeficient mice and perfused on day 68. Coating organoids with endothelial cells on day 34 produced robust vascularization after 3–5 weeks in vitro and 2 weeks in vivo, with CD31‑positive vessels observed inside and between rosettes, demonstrating the technical feasibility of patient‑specific vascularized brain organoids.

Abstract

The aim of this study was to vascularize brain organoids with a patient's own endothelial cells (ECs). Induced pluripotent stem cells (iPSCs) of one UC Davis patient were grown into whole-brain organoids. Simultaneously, iPSCs from the same patient were differentiated into ECs. On day 34, the organoid was re-embedded in Matrigel with 250 000 ECs. Vascularized organoids were grown in vitro for 3-5 weeks or transplanted into immunodeficient mice on day 54, and animals were perfused on day 68. Coating of brain organoids on day 34 with ECs led to robust vascularization of the organoid after 3-5 weeks in vitro and 2 weeks in vivo. Human CD31-positive blood vessels were found inside and in-between rosettes within the center of the organoid after transplantation. Vascularization of brain organoids with a patient's own iPSC-derived ECs is technically feasible.