Midkine increased blood vessel growth around cardiac cell grafts in animal experiments
Midkine increased blood vessel growth around cardiac cell grafts in animal experiments
On July 31, researchers published a study of human cardiac progenitor cells transplanted into injured pig hearts. The cells secreted Midkine. When the authors increased its production, endothelial cells migrated faster in culture, and vascular density increased in a mouse model.
A cell graft in the heart depends on the host’s blood supply. Blood vessels must grow into the new tissue to provide oxygen and nutrients. Transplanting the cells is therefore not enough. They also need a way to attract the cells that line blood vessels.
In a study published in Nature Cardiovascular Research, the team injected human cardiovascular progenitor cells into injured pig hearts. The researchers then examined tissue sections at several timepoints after transplantation using spatial transcriptomics, a method that shows which genes are active in particular cells and where those cells are located within the tissue.
The grafted cells produced increasing amounts of Midkine, an intercellular signaling protein. Midkine served as the signal through which the graft attracted blood vessels from the host. When the authors made the cells produce more of this protein, endothelial cells, which form the inner lining of blood vessels, migrated toward them more actively in culture. In a mouse model of ischemia-reperfusion injury, the density of CD31-positive vessels increased. CD31 is used as a marker of endothelial cells in tissue sections.
In a 2023 study, the same group injected approximately 200 million of these progenitor cells into injured pig hearts. After 12 weeks, the graft region contained 125% more CD31-positive vessels than the infarct region. The new article identifies a specific protein that may account for this recruitment of blood vessels.
Midkine had already been linked to collateral artery growth in mice. The protein affects the availability of VEGFA and the production of nitric oxide synthases. A 2018 study helps explain why Midkine may have contributed to the vascular response. Midkine levels can now be assessed as a property of a cell graft, alongside graft survival and cardiac function.