Human vascular organoids created from stem cells
Melero Martin Lab at Boston Children’s Hospital
A new method using small, lab-grown vascular structures has effectively restored blood flow to injured tissue in mice, significantly reducing necrosis. This technique shows promise for mitigating damage caused by injuries or blood clots in the future.
Previously, researchers developed vascular organoids by immersing human stem cells in a mix of chemicals, a process that took weeks and often resulted in structures that did not accurately replicate natural blood vessels, according to Juan Melero-Martin from Harvard University.
In a new approach, Melero-Martin and his team genetically modified human stem cells derived from reprogrammed skin cells. By introducing a genetic sequence and the antibiotic doxycycline, they were able to create vascular organoids in just five days. “The resulting blood vessels exhibited protein and gene activity levels closely resembling those of natural human tissues,” notes Melero-Martin.
To evaluate the organoids’ ability to rehabilitate damaged tissue, the researchers surgically obstructed the blood supply to one leg of several mice, reducing blood flow to less than 10% of normal. After an hour, they introduced 1,000 organoids at the injury site.
Two weeks post-implantation, imaging revealed that the new blood vessels had integrated with the existing ones, restoring blood flow to approximately 50% of normal levels, as stated by Oscar Abiles at Stanford University. “In cases of heart attacks, restoring even this amount of blood flow can significantly minimize tissue damage.”
Post-treatment, about 75% of the mice exhibited minimal dead tissue, while in a control group without organoid treatment, nearly 90% experienced severe tissue death.
In additional trials, the team treated mice with type 1 diabetes with organoids, which had caused pancreatic damage and elevated blood glucose levels. They discovered that integrating organoids with pancreatic tissue transplantation greatly enhanced glycemic control compared to transplantation alone.
However, further studies involving larger animals such as pigs are essential before considering human trials, Abirez states. Melero-Martin anticipates that human research could begin within five years.
Besides facilitating tissue repair, these findings may lead to the development of lab-grown mini-organs that more accurately represent bodily functions or even mini-tumors for research and treatment testing.
“Until recently, organoids lacked blood vessels and could only grow to a limited size. Beyond a few millimeters, they began to perish,” explains Abirez. “This study offers a method to incorporate blood vessels into organoids, thus enhancing their fidelity to human physiology and aiding treatment development.”
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Source: www.newscientist.com