Vascular organoids may be an effective treatment for ischemic heart disease

Ischemic heart disease (IHD), also known as coronary artery disease, is a leading cause of death and morbidity in western countries. IHD arises when blood vessels of the heart become clogged, blunting oxygen and nutrient supply to heart muscle cells, which eventually die off, leading to heart attack or heart failure. Although larger blood vessels can be replaced surgically to restore blood flow, there is currently no treatment targeting smaller blood vessels, so-called microvessels, which are essential for the uniform blood circulation within the heart muscle. 

Yasuhiro Shudo and his team from Stanford University, USA have tested a method to regenerate microvessels in the heart with stem cell-derived vascular organoids. Their work was published today in Stem Cell Reports.

Shudo's team set off by making vascular organoids, which are small aggregates of cells capable of forming new blood vessels, from endothelial progenitor cells (EPCs) isolated from human blood and mesenchymal stem cell-derived smooth muscle cells (SMCs) from human bone marrow. The team then placed patches of vascular organoids onto the outer heart surface of pigs with IHD and followed them for four weeks. Encouragingly, heart function in pigs receiving organoid patches was improved compared to untreated animals, and progression of IHD towards heart failure was mitigated. The organoid patches survived for several weeks and individual cells from the surface patches were found in deeper layers of the pig hearts suggesting they are migrating into the heart. The organoid patches also indirectly stimulated the pig hearts to make new microvessels and may have contributed to preserving heart muscle cell viability by releasing proteins that support cell survival. Collectively, these effects led to a measurably higher microvessel density and maturity in the transplanted hearts.

This proof-of-concept study shows that vascular organoids generated from an accessible source of human stem cells may be an effective treatment for IHD in a large animal model with similar heart size and physiology to the human heart. Future safety and efficacy studies will need to be performed before a similar treatment may become available to IHD patients in the future.