Blood vessel organoids support blood flow and tissue healing

Blood vessels grown in the lab in five days helped to restore blood flow and reduce tissue damage in mice.

Researchers have previously created blood vessels in vitro, known as vascular organoids, by exposing stem cells to different chemicals and transcription factors. However, this process usually takes several weeks and generates immature vascular organoids with limited use in the body. In a new study, researchers have developed a new method of creating vascular organoids that is faster with improved functionality.

Dr Juan Melero-Martin, from Boston Children's Hospital in Massachusetts, who led the research told New Scientist: 'We managed to get blood vessel organoids in just five days'.

One of the major challenges with successfully generating vascular organoids is the difficulty of getting the two main blood vessel cell types, endothelial cells and mural cells, to develop in a synchronised way. Dr Melero-Martin's team designed a new system that used the coordinated activation of two transcription factors, called ETV2 and NKX3.1. Using this system, induced pluripotent stem cells were developed into either endothelial cells or mural cells and formed blood vessels when in the presence of the antibiotic doxycycline.

Publishing their findings in the journal Cell Stem Cell, the authors explained: 'The potential for rapid, efficient, and controlled vascular differentiation makes this transcription factor-based approach to generating vascular organoids a promising avenue for addressing critical needs in vascularised tissue engineering and therapeutic applications.'

The next step was to test whether the vascular organoids could be used to treat tissue injuries in mice. To do this, the researchers carried out surgery on several mice to restrict the blood supply to less than ten percent of normal in one leg. One hour after the surgery, 1000 vascular organoids were implanted into each injury site.

When imaging the mice two weeks later, the team found that the implanted vascular organoids had connected with the existing blood vessels in the mice and restored the blood supply to around 50 percent of normal levels. Around 75 percent of the mice that received implanted vascular organoids had minimal tissue damage, whereas most of the leg tissue died in 90 percent of mice that were injured and not given the vascular organoids.

In a follow-up experiment, the researchers implanted the vascular organoids into mice with type 1 diabetes where damage to the pancreas causes high blood sugar levels. The results showed that implanting the vascular organoids into the mice alongside transplants of pancreatic tissue led to improved blood sugar control, compared with only transplanting pancreatic tissue.

The next step for the researchers is to conduct similar experiments with the vascular organoids in larger animals. If successful, Dr Melero-Martin believes that human studies could be performed within five years, with the new approach representing a significant advance in the development of vascular organoids, which may be used in the future as a treatment to reduce tissue damage caused by blood clots or accidents.