TY  - JOUR
A1  - Schmidt, Sven
A1  - Alt, Yvonne
A1  - Deoghare, Nikita
A1  - Krüger, Sarah
A1  - Kern, Anna
A1  - Rockel, Anna Frederike
A1  - Wagner, Nicole
A1  - Ergün, Süleyman
A1  - Wörsdörfer, Philipp
T1  - A blood vessel organoid model recapitulating aspects of vasculogenesis, angiogenesis and vessel wall maturation
JF  - Organoids
N2  - Blood vessel organoids are an important in vitro model to understand the underlying mechanisms of human blood vessel development and for toxicity testing or high throughput drug screening. Here we present a novel, cost-effective, and easy to manufacture vascular organoid model. To engineer the organoids, a defined number of human induced pluripotent stem cells are seeded in non-adhesive agarose coated wells of a 96-well plate and directed towards a lateral plate mesoderm fate by activation of Wnt and BMP4 signaling. We observe the formation of a circular layer of angioblasts around days 5–6. Induced by VEGF application, CD31\(^+\) vascular endothelial cells appear within this vasculogenic zone at approximately day 7 of organoid culture. These cells arrange to form a primitive vascular plexus from which angiogenic sprouting is observed after 10 days of culture. The differentiation outcome is highly reproducible, and the size of organoids is scalable depending on the number of starting cells. We observe that the initial vascular ring forms at the interface between two cell populations. The inner cellular compartment can be distinguished from the outer by the expression of GATA6, a marker of lateral plate mesoderm. Finally, 14-days-old organoids were transplanted on the chorioallantois membrane of chicken embryos resulting in a functional connection of the human vascular network to the chicken circulation. Perfusion of the vessels leads to vessel wall maturation and remodeling as indicated by the formation of a continuous layer of smooth muscle actin expressing cells enwrapping the endothelium. In summary, our organoid model recapitulates human vasculogenesis, angiogenesis as well as vessel wall maturation and therefore represents an easy and cost-effective tool to study all steps of blood vessel development and maturation directly in the human setting without animal experimentation.
KW  - organoid
KW  - blood vessel
KW  - vasculogenesis
KW  - angiogenesis
KW  - induced pluripotent stem cells
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284043
SN  - 2674-1172
VL  - 1
IS  - 1
SP  - 41
EP  - 53
ER  -