Engineered Organoid Technology

Organoids are miniature three-dimensional tissue cultures derived from stem cells that mimic the structure and function of real organs. Currently, engineered organoids have made progress in many aspects, including cells, microenvironments, multi-tissues, and functional readouts. These advances have significantly improved the utility of organoids in disease modeling, drug testing, and regenerative medicine.

1. Cellular level:

At the cellular level, researchers focus on optimizing the differentiation of stem cells, such as pluripotent stem cells or adult stem cells, into the specific cell types that make up the target tissue or organ. Fine-tuning this process could create organoids that more accurately represent the cellular diversity and complexity of real organs. For example, brain organoids derived from neural progenitor cells now feature neurons, astrocytes, and oligodendrocytes, increasing their use in neurodegenerative disease research.

2. Microenvironment level:

The microenvironment refers to the microenvironment surrounding cells, which affects cell behavior and development. Designing this microenvironment by using biomaterials such as hydrogels or extracellular matrix components helps the organoids form more structured and organized tissues. Optimization of this microenvironment facilitates organoid survival, growth, and maturation, as well as accurate modeling of organ development or disease progression.

3. Multiple organizational levels:

At the multi-tissue level, the aim is to integrate multiple tissue types into a single organoid system. This approach is particularly important for building organ systems where different cell types interact, such as liver or heart organoids. In addition, co-culture of various cell types can achieve more accurate inter-tissue signaling and tissue-level functions, allowing for in-depth understanding of complex diseases.

4. Functional level:

Improving functional levels can enhance the physiological response of organoids to better mimic real organ function. This includes creating more reliable electrical activity in cardiac organoids, enabling fluid transport in kidney organoids, and even developing vascularization in complex organoids. These advances could help measure how closely organoids function like actual organs, improving their use in drug testing and personalized medicine.

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Reference

[1] Moritz Hofer and Matthias, Nature Reviews Materials 2021 (https://doi.org/10.1038/s41578-021-00279-y)