Scientists show organ chips. Image source: Kevin Monko
It looks like a small ball with irregular cells gathered together under the microscope. The mini organs cultured in these laboratories have a very complex structure: tiny tubules on the kidneys, cerebral cortex or subtle folds in the intestines.
Now, with 3D cell culture technology, scientists have been able to create a variety of organs in the laboratory, including the liver, pancreas, stomach, heart, kidney, and even the breast. These multicellular structures, although not truly organs, have become ideal tools for studying human development and disease.
With the advancement of science and technology, organ-like technology has opened up frontiers in biomedical research. For example, the technology can perform anticancer drug testing on cells from specific patients, but there are still problems to be solved, including the production and control of organoids and their microenvironmental analysis.
Recently, Science launched a special issue to discuss the design and application of organoids, the next generation of organs and organ technology on the chip.
“The growth and development of organs are very similar to human organs, but small enough to fit in Petri dishes. Organs can allow researchers to reflect the inside of the body in a more realistic way. But as they develop, classes Organs may be more difficult to control, and this variability may have an impact on the precise control properties of the study." Dongeun Huh, a bioengineer at the Department of Bioengineering at the University of Pennsylvania, told the Chinese Journal of Science.
Sophisticated design
Although organoids can structurally mimic the fine structures inside many organs, they have many differences with real human organs, the most important of which is the lack of vascular system, and the blood is responsible for maintaining the growth and development of human organs. Features are essential. Therefore, the organ can only be in a mini and simple state forever.
Organoids are multicellular structures derived from adult or pluripotent stem cells. Because these organs reflect the growth of organs during the first few weeks and months, they can help researchers identify "glitches" that occur during these processes.
The University of Cambridge research team developed a "mini placenta" with cells from the placental villi. This experimental model, called the organoid, survives for a long time, is genetically stable, and secretes related proteins and hormones, which is very similar to normal placenta in the first trimester, and even positive in pregnancy tests. It will open a window for the study of early pregnancy to help explore the causes of pregnancy failure and related diseases.
James M. Wells, a developmental biologist at the Department of Developmental Biology at the Children's Hospital of Cincinnati, and his collaborators, used human pluripotent stem cells to grow intestinal tubular tissue and added growth factors, successfully initiating related gene codes to promote cell development and formation of human colonic organs. . After 6 to 10 weeks of transplantation into experimental mice, the morphology, structure, molecular and cellular characteristics of this type of organ are similar to those of human colon.
"You can see that congenital deficiency occurs in the petri dish in front of your eyes," Wells said.
However, Wells also said that the current challenge of organ design is to transform the complexity of cells into organoids in a controlled manner, thus achieving orderly assembly and acquisition of tissue functions. “We have been discussing how to design next-generation organoids through engineering-based 'description methods' to control assembly, morphogenesis, growth, and function.â€
Engineering "narrative" organs
The engineering principle of controlling organogenesis is to describe the "consensus initiative" of engineering. Takanori Takebe of the Cincinnati Children's Hospital Medical Center said that the concept first appeared in insect biology to explain social behavior, a form of indirect communication - the context of the individual, the coordination of the environment and interdependence, The indirect effects of past behavior.
Dynamic multicellular self-assembly of organoids requires the conversion of this consensus initiative factor into engineering drivers, which is not a common goal of typical tissue engineering concepts. Takebe mentioned that scientists interpret this concept as a self-organizing biological system closely related to history or memory, that is, the morphogenesis of a cell population is not only affected by current conditions, but also by previous events.
In other words, the self-organization of organisms comes from the gradual local interactions between cells, which were originally disordered systems caused by environmental fluctuations, which were later amplified by positive feedback.
Controlling biological history (or “storyâ€) in biological systems benefits from an overall design strategy based on multiple evolutionary engineering-driven principles, including tissue engineering, synthetic biology, biomanufacturing, biomaterials, and computational models. Among them, organ chip technology is a high-profile direction.
Huh said that although the class function is more accurate in modeling the human body than the chip organ technique, the organoids develop in a highly variable manner, making it difficult to control.
Organ on the chip
Huh's research focuses on creating organs on the chip: a special micro-device made of human cells that mimics the natural cellular processes of the organ. Huh Labs designed chips that mimic the function of the placenta and lung disease.
Lin Bingcheng, a researcher at the Dalian Institute of Chemical Physics of the Chinese Academy of Sciences and a professor at Dalian University of Technology, used microfluidic organ chip technology to break through the limitations of artificial kidney simulation and developed a new generation of artificial kidneys, including glomeruli, small blood vessels, and renal capsules. Ten structural and functional bionic designs, such as renal blood flow and renal urinary flow, can completely simulate the entire blood purification process. The researchers used the artificial chip kidney to identify cisplatin in vitro, which can cause tubular toxicity, doxorubicin-induced glomerular toxicity, and achieve in vitro nephrotoxicity of the drug.
In an interview with the Journal of Chinese Academy of Sciences, Yan Duanqing, a researcher at the Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, said that organ chips may be able to replace animal experiments and become a promising research tool.
The integration of organoids and chip organ technology may help the better use of organoids in biomedical applications, such as testing scenarios that cannot be tested in humans.
"We can use a chip organ device to control cells in the microenvironment with great precision, and combine the true physiological conditions of the organ-like organs with the control and reproducibility of the chip organ technology to develop a more advanced system. Both eclectic and eclectic," Huh said.
In addition, Wells believes that the next generation of organ culture should also focus on integrating key cell types that are shared among many organs, such as blood vessels, lymphatic vessels, nerves, stromal cells, and immune cells. In the case of organogenesis, vascular cell types and nerve cells can be produced separately and introduced into the organoids during the time of embryonic organogenesis, near their normal arrival.
This method can introduce blood vessels into the brain and liver organs, introduce interneurons and microglia into brain organs, and provide a functional enteric glial plexus for intestinal organs to control their peristalsis.
Related paper information:
DOI: 10.1126/science.aaw7567
DOI: 10.1126/science.aaw7894
Source: Chinese Journal of Science
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