This two-week-old heart organoid – with cardiomyocytes (green) and smooth muscle cells (white) – is surrounded by endothelial cells (magenta) that form a network of realistic blood vessels.
Two separate teams of researchers have found a way to grow blood vessels within lab-grown organs.
The creation of miniature organs in the lab, such as tiny replicas of hearts, livers, and lungs, has been a focus for scientists.
These structures, called organoids, have advanced how we study disease and test new drugs.
But there’s always been a missing piece to this puzzle: blood vessels.
The organs rely on a constant supply of blood, nutrients, and oxygen to work properly.
Without these networks, lab-grown organoids couldn’t grow to a significant size, function fully, or mature completely. For instance, a mini-kidney couldn’t filter blood effectively, nor could a mini-lung exchange gases, without the necessary vessel systems.
Just this past month, two new studies published in the journals Science and Cell have announced a game-changing new approach to tackle this challenge.
Nature reported it could allow researchers to grow blood vessels concurrently with organ tissue, right from the initial developmental stages, rather than trying to incorporate them in later stages.
It all starts with pluripotent stem cells – the body’s master cells, capable of transforming into almost any cell type.
The researchers are now coaxing these incredible cells to form both the organ tissue and the blood vessels at the same time.
To address the lack of blood vessels in lab-grown organs, the team from the University of California first attempted to assemble components separately.
They used fluorescent markers to differentiate cell types, expecting red for blood vessels and green for lung tissue, which would then be combined.
Embryonic mouse lung showing blood vessels (white) and air sacs (pink).
However, they were surprised to find that both red-colored vascular networks and red-colored epithelium (lung tissue) were developing simultaneously from the same starting material.
Reportedly, these were often seen as “contaminants,” but researchers explored how to amplify the process.
They developed a new strategy that allows lung tissue and blood vessels to grow together from the outset, mimicking natural lung development more closely.
This approach resulted in mini-organs with greater cell diversity, better 3D structure, improved cell survival, and more mature development compared to previous models.
Upon transplantation into mice, the new lung organoids matured to form diverse cell types and even created alveolar sacs vital for gas exchange.
The research team immediately put their improved mini-lung models to practical use. They began studying Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV), a rare and often fatal lung disorder affecting newborns, which is caused by mutations in the FOXF1 gene.
Meanwhile, in a parallel effort, researchers at Stanford Medicine, led by Dr. Oscar Abilez, also achieved significant success.
They focused on growing heart and liver organoids complete with their own tiny, functional blood vessels.
Abilez’s team aimed to optimize a chemical “recipe” to reliably generate nearly all the cell types found in the human heart, including a blood vessel network.
They combined established methods for creating cardiomyocytes, endothelial cells, and smooth muscle cells, testing 34 different combinations of growth factors and other molecules.
After two weeks of growth, one recipe, “condition 32,” proved to be exceptionally effective. It produced colorful cardiac organoids, indicating a high abundance of cardiomyocytes, endothelial cells, and smooth muscle cells.
Under 3D microscopy, these successful doughnut-shaped organoids revealed an organized structure: cardiomyocytes and smooth muscle cells on the inside, surrounded by an outer layer of endothelial cells forming distinct, branching blood vessels resembling capillaries.
Even more surprisingly, single-cell RNA sequencing analysis of these organoids uncovered nearly all the other cell types present in a human heart.
“It had all these other cell types that are found in the heart,” Abilez said. “That was unexpected in a positive way.”
These studies in growing vascularized organoids represent a major step forward in studying human development and disease.
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