Blood vessel organoids quickly minimise damage to injured tissue

Tiny blood vessels cultivated in the laboratory helped restore blood flow to wounded tissues in mice, minimizing necrosis. This approach could one day be used to reduce some of the damage caused by accidents or blood clots.

The researchers have already made tufts of blood vessels cultivated in the laboratory, called organoids, by immersing human stem cells in a cocktail of chemicals. But this approach takes a few weeks and often produces vessels that badly imitate those of the body, explains Juan Melero-Martin at Harvard University.

In an alternative approach, Melero-Martin and its genetically modified colleagues of human stem cells which have been manufactured by reprogramming skin cells. They gave stem cells a genetic sequence that makes them develop in blood vessels in the presence of antibiotic doxycycline. “We managed to obtain blood vessel organs in just five days,” said Melero-Martin. The vessels also had levels of protein and gene activity very similar to those found in the human body, he says.

To test if their organoids could treat wounded tissues, the researchers surgically cut the blood supply to one leg of several mice, so it was less than 10% of normal levels. An hour later, they set up 1000 organoids on each of the injury sites.

During the mouse imagery two weeks later, the team found that the bloody vessels implanted had merged with those already in animals, restoring blood supply at 50% of normal levels – a substantial quantity, explains Oscar to abiler at the University of Stanford in California. “For example, in a heart attack situation, if you can restore so many blood flows to tissues, in reasonable time, this would be significant to reduce tissue damage.”

After treatment, around 75% of animals had a minimum level of dead fabric, explains Melero-Martin. Among those who were injured and not given by the blood vessels implanted, most of the leg tissue died in around 90% of individuals.

In another experience, researchers have used organoids to treat mice with type 1 diabetes, where damage to pancreas make blood sugar become too high. They found that the implantation of organoids in mice along the transplants of the pancreatic tissue has considerably improved their control of blood sugar, compared to the pancreatic tissue of transplanting alone.

But other studies on larger animals such as pigs are necessary before the approach can be tested in people, explains Abilez. Melero-Martin says that the team hopes to do so, adding that human studies could take place realistically within five years.

In addition to treating tissue lesions, the results could help the development of mini-organizations cultivated in the laboratory which better imitate what is happening in the body or even mini-tumons that scientists can study and test the treatments in the laboratory.

“Until recently, these organoids can only reach a certain size, because they do not have blood vessels – therefore, after a certain size, a few millimeters, they begin to die,” explains Abilez. “This study offers a means of adding blood vessels to these organoids so that they better represent the physiology of a human and are more useful for developing treatments.”