A mini organ grown in a petri dish has begun to generate its own blood vessels. The kidneys require blood vessels to perform their function of filtering blood. Now, the mini kidneys, hearts, and lungs are not only shaped like actual organs but also mimic their functions.
Researchers at the Stanford University Cardiovascular Institute, led by Joseph Wu and Oscar Abilez, announced on 5th that they have created heart and liver organoids with their own blood vessels for the first time, as reported in the international journal Science. The research team at the Beijing Stem Cell Research Institute in China also reported on 30th that they succeeded in cultivating lung organoids while allowing blood vessels to grow alongside them.
◇Mini hearts create blood vessels in the lungs
Organoid is a new term formed by adding the suffix (-oid) meaning 'similar to an organ'. It is cultivated from stem cells, which can grow into all cells of the human body, into a three-dimensional structure similar to an organ and is referred to as a mini organ. Previously, cells were mainly grown in flat petri dishes, failing to accurately reflect how cells arrange, move, and interact within the body.
The Stanford research team created heart and liver organoids from stem cells, the primitive cells that grow into all cells of the human body. They induced the cells to form blood vessels in the process. Previously, they had cultured cells that would become blood vessels separately or printed blood vessels using a 3D printer and combined them with heart organoids, but they could not create organoids with a complete blood vessel system.
The research team reviewed existing methods that generate three main cell types: cardiomyocytes, endothelial cells, and smooth muscle cells. Cardiomyocytes and smooth muscle cells compose the heart, while endothelial cells form the blood vessels. They created 34 different culture conditions by varying the types and amounts of growth factors. Blood vessels were generated under the 32nd condition.
The researchers observed donut-shaped heart organoids under the microscope. Inside were arranged cardiomyocytes and smooth muscle cells, while outside were endothelial cells that formed blood vessels. The blood vessels formed had a diameter similar to that of a human hair, ranging from 10 to 100 μm (micrometers, where 1 μm is one millionth of a meter), resembling the capillaries of a real heart.
◇Replacing animal experiments and enabling cell therapy
The research team at the Beijing Stem Cell Research Institute induced blood vessels in the lung organoids. They cultured epithelial cells that would become the lung and blood vessel cells simultaneously. The signals that promote growth in the two types of cells differ at the development stage. Dr. Yifei Miao noted that "to nurture one side, the other has to be sacrificed, so they cannot grow together naturally," adding they discovered a method to control the timing of administering a molecular cocktail mixed with various substances that regulate development to enable the simultaneous formation of two types of tissues from stem cells.
The lung organoids transplanted into mice matured into various cell types, including alveoli where gas exchange occurs. The researchers explained that the blood vessel cells allowed for a spontaneously formed structure similar to alveolar sacs.
Although the organoids are small, they share the same three-dimensional structure as actual organs, making them capable of replacing existing human cell experiments. Additionally, since they are human cells, they provide a more accurate representation of human responses compared to animal experiments. The U.S. Food and Drug Administration (FDA) recognized organoids as an alternative technology to animal testing last April.
However, while organoids have closely mimicked the shape and structure of organs, they have not yet achieved the capability to fully implement human metabolism due to the lack of their own blood vessels. The kidneys must have blood vessels to filter blood and produce urine, and the lungs must have blood vessels to exchange oxygen and carbon dioxide. If organoids possess blood vessels, they will be able to demonstrate not only cellular responses but also changes in organ function.
The Stanford team expressed that they could pave the way for regenerative therapies using organoids in the future. Professor Joseph Wu predicted that in the future, heart organoids with blood vessels could be cultured from patients' own stem cells to replace damaged tissues. Dr. Abilez mentioned that "if the transplantable organoids have a blood vessel system, it could enhance the likelihood of survival by connecting with the original organ's blood vessels."
◇The need for modular organoid technology
However, organoids with blood vessels have only implemented initial stages of development seen in fetal development. They are not in a mature organ state. Even with blood vessels, the mini organs must be able to circulate blood to fulfill their primary functions. Scientists have pointed out that modular technology, which connects multiple organoids, is also necessary for them to function like real organs.
For example, testing drugs for kidney disease requires both kidney organoids and liver organoids. Since drugs are processed in the liver, both organoids need to be present to understand the efficacy and side effects of the medication. A heart organoid capable of circulating blood is also necessary.
Scientists are already investigating real human responses more accurately using assemblyloid technology. Sergiu Pasca, a professor at Stanford University Medical School, reported last May that he implemented the human pain signal transmission pathway using brain assemblyloids.
Professor Pasca cultured sensory neurons to the spinal cord, thalamus, and cerebral cortex, each in separate organoids. After placing the organoids together for 100 days, the nerve cells connected and grew into sausage shapes. An assemblyloid demonstrating the ascending sensory pathway was born. When capsaicin, which induces a burning sensation, was injected into the assemblyloid, nerve signals were generated in sequential order along the sensory pathway.
References
Science (2025), DOI: https://doi.org/10.1126/science.adu9375
Cell (2025), DOI: https://doi.org/10.1016/j.cell.2025.05.041
Nature (2025), DOI: https://doi.org/10.1038/s41586-025-08808-3