Advancements in Stem Cell Research: Creating Vascularized Organoids
by Micaela Harris-Kim
July 22, 2025
In the past decade, human pluripotent stem cells have been a transformative technology in the world of biomedical research. Researchers have found that not only can these stem cells differentiate into most any other cell type in the human body, but they can also be used to create organoids, which are millimeter-size structures that mimic key organ functions. Although several studies have shown that many types of these organ-like structures hold therapeutic promise, it has remained challenging to form blood vessel-like structures within organoids.
A team at Stanford University and the University of North Texas led by co-first authors Oscar Abilez, MD, PhD, Huaxiao Yang, PhD, and co-corresponding author Joseph C. Wu, MD, PhD, conducted a new study designed to co-create blood vessels within heart and liver organoids using human pluripotent stem cells, recently published in Science1. The investigators differentiated human pluripotent stem cells into heart and liver organoids and used a novel combination of growth to create a vascular network within the organoids. By using a combination of high-resolution imaging and single-cell transcriptomics, they compared the cellular composition of the heart organoids to human hearts, and found they had developed organoids that closely modeled the human heart early in development. This discovery allowed the team to observe how stem cells develop into different heart cell types over time and provided a safe method to study communication between cells without requiring human patients.
Organoid made up of heart cells in green, smooth muscle cells in white, and blood vessels in magenta. Reprinted with permission from O.J. Abilez et al., Science 388, eadu9375 (2025).
An additional breakthrough of this study was the creation a new triple reporter stem cell line, which is a cell line that has been genetically engineered to express three different fluorescent reporter proteins that identify heart cells and two types of blood vessel cells. This new reporter line enabled the investigators to visualize the formation of the blood vessels intermixed with the heart and liver cells that are seen in organ development.
By optimizing the stem cell experimental conditions for differentiation, the researchers successfully generated vascularized heart and liver organoids in a scalable and reproducible way. Through continued innovation of this model, it is envisioned that human pluripotent stem cells can be used to create vascularized organoids and ultimately support successful therapeutic interventions.
Additional Stanford Cardiovascular Institute-affiliated investigators who contributed to this work include Mengcheng Shen, Zehra Yildirim, Yan Zhuge, Ravichandra Venkateshappa, Shane R. Zhao, Logan Dunkenberger, Lei Tian, Kitchener D. Wilson, Fangjun Jia, Hung Ta Wo, Ioannis Karakikes, and Christopher K. Zarins.
1. https://www.science.org/stoken/author-tokens/ST-2659/full
Abilez OJ, Yang H, Guan Y, Shen M, Yildirim Z, Zhuge Y, Venkateshappa R, Zhao S, Gomez AH, El-Mokahal M, Dunkenberger L, Ono Y, Shibata M, Nwokoye P, Tian L, Wilson KD, Lyall EH, Jia F, Wo HT, Zhou G, Aldana B, Karakikes I, Obal D, Peltz G, Zarins CK, Wu JC. Gastruloids enable modeling of the earliest stages of human cardiac and hepatic vascularization. Science, 2025 Jun 5;388(6751):eadu9375. doi: 10.1126/science.adu9375. Epub 2025 Jun 5. PMID: 40472086.
Dr. Oscar Abilez