Generation of human 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.

Grow your own brain

“…Researchers have also developed ways to vascularize the organoids [7]. Taking a standard, stem cell-derived cerebral organoid and surrounding it with their newly developed endothelial cells, researchers grew an organoid that contained capillaries that penetrated its inner layers (Figure 4).…”

Recreating Physiological Environments In Vitro: Design Rules for Microfluidic‐Based Vascularized Tissue Constructs

“…Vascularization of these so‐called “mini‐brains” are particularly important for the study of late brain development as the current models develop a necrotic core without the vasculature to supply oxygen and nutrients and thus cannot survive past the embryonic stage . Although these human brain organoids can be xenotransplanted into mice skulls and vascularized by resident mouse cells, such a chimeric organoid construct remain distinct from the human organ, and is not suitable for studying human regenerative medicine and human biology . Ideally, a vascularized brain organoid model that is composed of entirely human cells could be constructed by integrating the vascular network and the brain organoid in a microfluidic chip.…”

The Emergence of Stem Cell‐Based Brain Organoids: Trends and Challenges

“…Importantly, this procedure has resulted in neuronal maturation in organoids. Pham et al took an alternative approach by coculturing organoid. Surprisingly, this approach has resulted in vascularization within organoids even before implanting them into a host mouse.…”