Vascular Organoid Patches Help Regenerate Blood Vessels in Pigs

Ischemic heart disease (IHD), also known as coronary heart disease, is the leading cause of death and morbidity in the United States.¹ In its most severe form, blood vessels become narrowed or blocked, resulting in inadequate blood flow, and leading to heart muscle cell dysfunction. Although larger, damaged blood vessels can be surgically replaced, there is no current treatment for the affected smaller microvessels within the heart.

This lack of treatment motivated cardiothoracic surgeon Yasuhiro Shudo and his colleagues at Stanford University to create vascular organoids derived from human cells capable of forming new blood vessels. In a new paper, published in Stem Cell Reports, the researchers transplanted patches of vascular organoids on the surface of hearts from pigs with IHD.² These patches helped to promote new microvessel growth and improve heart function. This proof-of-concept study demonstrated the therapeutic applications of human-derived vascular organoids.

Rather than relying on a single cell type, the researchers co-cultured two cell populations: endothelial progenitor cells, which are highly proliferative and can form vascular networks, and mesenchymal stem cell-derived smooth muscle cells, which have been used for heart tissue repair. In an earlier study, Shudo and his colleagues successfully transplanted these human-derived vascular organoids into rodents.³

In the current study, the team evaluated the therapeutic potential of vascular organoid patches in pigs with IHD. They surgically implanted the organoids onto the surface of the left ventricular wall and found that the patches survived for several weeks. Cells from the transplanted organoids also migrated from the heart's surface into deeper layers of the organ.

Untreated pigs experienced progressive deterioration in heart muscle thickness and function. Meanwhile, pigs that received the organoid patches showed improved blood flow and preserved cardiac function. Then, the researchers used immunohistochemical staining and further confirmed that the transplanted organoids engrafted within the heart tissue and promoted the formation of new microvessels, led to increased vessel density and enhanced vessel maturity. In addition, the team assessed gene expression changes that occurred from the organoids within the ischemic border zone, the region of tissue between the severely damaged and healthy heart muscle cells. Organoid-treated groups exhibited increased expression of angiogenesis-related genes.

Together, these findings suggest that vascular organoid patches could become a promising interventional therapy for restoring blood flow and preserving cardiac function in ischemic heart disease and heart failure.