Formation of Stable, Long Lasting 3D Blood Vessels from Endothelial Cells
Formation of Stable, Long Lasting 3D Blood Vessels from Endothelial Cells
Invention Summary
The inventors have discovered that overexpressing the transcription factor Etv2 in adult endothelial cells results in cells that are capable of forming fully functioning 3D blood vessels in vitro that are stable and long-lasting.
Technology Overview
Despite advances in the fields of angiogenesis and vasculogenesis, the technology to enable endothelial cells to grow in to fully functional 3D blood vessels in vitro has not yet been devised. The main approach thus far, has been to “force” endothelial cells to grow into blood vessels inside of pre-fabricated artificial scaffolds. However, these artificial blood vessels that are formed inside tunnel-like molds are not long lasting and lack a functioning lumen.
The inventors have addressed this major problem by identifying a key player in turning endothelial cells into blood vessels, theE-twenty-six specific sequence (ETS) transcription factorvariant 2 (ETV2). ETV2 is a master transcription factor that is transiently expressed from day E7.5 to E10.5 in mouse development, and plays a crucial role in the formation of the primary vascular plexus and vasculogenesis. The inventors have shown that transient overexpression of ETV2 in adult endothelial cells mediates the growth of long lasting functional 3D vessels, which can be used as a platform for vessel formation both in vitro and in vivo. The “reprogramming” of endothelial cells by a transcription factor that allows them to attain vasculogenic properties is a major advancement in the field.
Potential Applications
- This technology could be used as a platform to further understand and elucidate the biology behind vessel and lumen formation networks in endothelial cells.
- As a platform, this technology could also be used for screening various known and unknown drugs and compounds that can disrupt angiogenesis, by usingvascularized tumor organoids.
- ETV2 vessels could be used in animal injury models to replace damaged vasculature.
- A major problem with growing organs or organoids in vitro is that they lack proper vasculature, thus limiting their function and size. This issue could be addressed via this technology to ensure proper perfusion in preparation for organ transplantation.
Advantages
- The vessels are accessible and encapsulation free, allowing for easy manipulation.
- The vessels are highly stable for at least 16-20 weeks.
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