Scientists create organoids with specialized blood vessels

August 5, 2025

Scientists create organoids with specialized blood vessels

At a Glance

  • Scientists made mini-lungs and intestines, called organoids, that generate their own specialized blood vessels.
  • The organoids offer insights into how these organs develop and function, and could help reduce the need for using animal models in medical research.
Image
Microscope image showing six clusters of air sacs surrounded by blood vessels.
Embryonic mouse lung showing blood vessels (white) and air sacs (pink).
Hill Chang and Yifei Miao, UCLA

For more than a decade, researchers have been working to create tiny 3D structures called organoids that can mimic the structure and function of various organs. These little organoids generally form spheres smaller than a grain of rice. They鈥檝e been used to test drugs, assess potential therapies, and reveal the underpinnings of many disorders.

But to date, most organoids have lacked blood vessels or had only primitive ones. Blood supply is essential to organ health because it carries oxygen-rich blood and nutrients to organs and tissues, and ferries away waste. But the blood vessels, or vasculature, of different types of organs are specialized. A key challenge has been to create organoids that have blood vessels that simulate the vasculature of specific organs, such as lungs, heart, or liver. In earlier efforts, researchers tried to create vascularized organoids by growing organ and vascular tissues separately and then combining them at a later stage. But these assembled organoids failed to mimic cell-cell interactions during organ development or the organ-specific structure and function of the vasculature.

An 精东影业-supported research team led by Dr. Mingxia Gu of UCLA, formerly at Cincinnati Children鈥檚 Hospital Medical Center, aimed to develop and test a different approach. They devised a way to grow organ and blood vessels together from the start, at their earliest stages. Their recent work focused on creating vascularized lung and gut organoids. The study appeared in Cell on June 27, 2025.

The scientists began with human pluripotent stem cells, which can be coaxed to divide and transform into any cell type of the body. The team developed a method to co-create two of the three layers that arise during early development of humans and most animals. One is the endoderm, which eventually transforms into epithelial cells in lungs, digestive organs, and more. The other is the mesoderm, which gives rise to different types of blood cells and the inner lining of blood vessels.

Once they successfully grew these together, the team was able to add different cocktails to the tiny spheres to induce them to become vascularized lung or intestine organoids. These closely parallelled how the equivalent organs develop and behave in the human body. The researchers showed that the vascularized lung organoids could generate a wide range of lung-specific cell types, including tiny air sacs called alveoli. The blood vessels that developed in these organoids closely resembled those found in the specific human organs, with the unique features and functions of each tissue.

The team next used vascularized lung organoids to gain insights into a rare inherited lung disorder called alveolar capillary dysplasia with misalignment of pulmonary veins. It arises from a mutation in a gene called FOXF1. The disorder has been hard to study via conventional lung organoids because the defective gene mostly affects blood vessels and support cells. The scientists used stem cells from patients with FOXF1 mutations to grow vascularized lung organoids that mimic many of the blood vessel and lung abnormalities that arise in people with this disorder.

Organoids with organ-specific vasculature will help scientists better understand how blood vessels form and function in different parts of the body and what goes wrong in various diseases. They also offer a human-based system that may be more accurate for testing new drugs.

鈥淲e鈥檙e essentially opening a window into cell-cell crosstalk during the early stages of human development, an area where our knowledge has been limited,鈥 Gu says. 鈥淪cientists can now more effectively use human tissue models to study disease while reducing reliance on animal models to develop new medicines.鈥

鈥攂y Vicki Contie

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References

. Miao Y, Pek NM, Tan C, Jiang C, Yu Z, Iwasawa K, Shi M, Kechele DO, Sundaram N, Pastrana-Gomez V, Sinner DI, Liu X, Lin KC, Na CL, Kishimoto K, Yang MC, Maharjan S, Tchieu J, Whitsett JA, Zhang YS, McCracken KW, Rottier RJ, Kotton DN, Helmrath MA, Wells JM, Takebe T, Zorn AM, Chen YW, Guo M, Gu M. Cell. 2025 Jun 27:S0092-8674(25)00628-2. doi: 10.1016/j.cell.2025.05.041. Online ahead of print. PMID: 40592324.

Funding

精东影业鈥檚 National Heart, Lung, and Blood Institute (NHLBI), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and National Cancer Institute (NCI); Cincinnati Children鈥檚 Research Foundation; American Heart Association; Dr. Ralph and Marian Falk Medical Research Trust; Brigham Research Institute; Erasmus MC.