Organoids – tiny 3D cell structures – have long been used to study disease and test drugs. However, most organoids lack blood vessels, which limits their size, function, and maturity. For example, kidneys need blood vessels to filter blood, and lungs need them to exchange gases.
Last month, two independent research teams published in the journals Science and Cell how to create vascularized organoids from the very beginning. They started with pluripotent stem cells, then manipulated their differentiation to create both organ tissue and blood vessel cells.
“These models really show the power of the new approach,” said Oscar Abilez, a stem cell expert at Stanford University and co-author of the heart and liver study.
Initially, research teams often mixed blood vessel tissue and other tissue separately into an “assembloid” (a test-tube model combining many organoids or other cells), but this approach still did not fully reproduce the real structure.
The breakthrough came from a serendipitous discovery while cultivating epithelial cells, several research groups including the University of Michigan noticed that organoids spontaneously generate more vascular endothelial cells. Instead of eliminating them, they sought to “replicate” this phenomenon in intestinal organoids.
With that clue in mind, Yifei Miao and colleagues at the Institute of Zoology, Chinese Academy of Sciences , tried to control the co-development of epithelial cells and blood vessel cells in the same culture dish. Initially, this was difficult because the two cell types needed opposite molecular signals to grow. However, the team found a way to adjust the timing of adding stimulating molecules, allowing both to grow together.
As a result, the lung organoids, when implanted in mice, differentiated into many cell types, including cells specific to the alveoli – the site of gas exchange. When grown on a 3D scaffold, they self-arranged into alveolar-like structures. Josef Penninger, an expert at the Helmholtz Center for Infection Research (Germany), assessed this as an interesting step forward.
Similarly, Abilez created heart organoids that contained muscle cells, blood vessels, and nerves. Blood vessels formed small branches that snaked through the tissue. This approach also created miniature livers with many tiny blood vessels.
However, current organoids still only replicate the early stages of embryonic development. Penninger says that for organoids to function like real organs, scientists will have to develop larger blood vessels, supporting tissue, and lymphatic vessels. The next challenge is to “open the valves” for the blood vessels to carry actual flow. “This is an incredibly exciting area,” he says.
Source: https://baoquocte.vn/dot-pha-noi-tang-nhan-tao-tu-hinh-thanh-mach-mau-320722.html
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