Researchers from Stanford University, led by Yasuhiro Shudo, reported on Jul. 2 that they have tested a new method to regenerate microvessels in the heart using stem cell-derived vascular organoids. The findings were published in Stem Cell Reports.
Ischemic heart disease, also known as coronary artery disease, is a major cause of death and illness in western countries. The condition occurs when the blood vessels supplying the heart become blocked, reducing oxygen and nutrient delivery to cardiac muscle cells and potentially resulting in heart attack or failure. While surgical replacement can restore larger blood vessels, there are currently no treatments targeting the smaller microvessels that are critical for uniform circulation within the heart muscle.
Shudo's team created vascular organoids—small clusters of cells capable of forming new blood vessels—from endothelial progenitor cells isolated from human blood and smooth muscle cells derived from human bone marrow mesenchymal stem cells. These organoid patches were placed onto the outer surface of pig hearts affected by ischemic heart disease and monitored over four weeks.
The results showed improved cardiac function in pigs treated with organoid patches compared to untreated animals. Progression toward heart failure was reduced, and individual cells from the patches were found deeper within the pig hearts, suggesting cellular migration into cardiac tissue. The patches also appeared to stimulate native microvessel formation indirectly and may have helped preserve viability of existing heart muscle cells through protein release that supports cell survival. This combination led to higher density and maturity of microvessels in transplanted hearts.
The study demonstrates proof-of-concept that vascular organoids generated from accessible sources of human stem cells could be an effective treatment for ischemic heart disease in large animal models with physiology similar to humans. Further safety and efficacy studies will be required before such treatments can be considered for patients.
