A new automated system that is capable of producing organs from stem cells

Organoids: mini organs in a petri dish for disease research and new cures

A new automated system developed at the University of Washington is capable of efficiently producing mini organs from stem cells, and thereby has the potential to accelerate biomedical science and research.


Microwell plate containing kidney organoids generated by robots from stem cells.
Source: Freedman Lab/UW Medicine

Normally, when a researcher wants to test medications or treatments on cells from a particular tissue - for example, a liver - he should first grow the cells in the laboratory in a petri dish. The cells grow on the bottom of the dish and form a thin two-dimensional tissue that does not reflect what happens in the complex three-dimensional tissue that exists in the body. In recent years, researchers have been able to make stem cells develop into three-dimensional structures more like those in the body, called mini-organs. Researchers are able to test different treatments for the mini-organs, and to be more confident that they actually reflect what happens in the living body.

But there is one big problem: producing mini-organs is a time consuming and labor intensive task. First, the cells should be seeded in the petri dishes, its culture medium (liquid or gel designed to support the growth of microorganisms) should be changed every day, the dishes should be monitored to make sure they do not contaminate, and the stem cells that begin to differentiate into mini-organs should be identified. This is an expensive and laborious work - and as such, it hampers research advances. Researchers who want to try to expose the mini-organs to hundreds of different chemicals must first produce thousands of such mini-organs on their own in a short time - a task that is almost impossible to perform without mistakes on the way.

That was the reason for the new study at the University of Washington, where researchers for the first time demonstrated a completely automated system for producing organoids. The robots seeded the stem cells into dishes that contained as many as 384 miniature wells each, and then nurtured them to turn into kidney organoids over 21 days. Each little micro-well typically contained ten or more organoids, and each plate contained thousands of organoids, that otherwise would require the intensive work of a researcher for a whole day. The robot, on the other hand, did the work in twenty minutes - and performed it without any effort, without getting tired or making any mistakes.

The researchers further trained robots to process and analyze the organoids they produced. Researchers at the University of Michigan collaborated with researchers at the University of Washington, and demonstrated how another robotic system uses a technique called single cell RNA sequencing to identify all the different types of cells found in the mini-organs.

Such automation of the study should allow researchers, as mentioned, to easily test many ideas on a myriad of mini-organs. It is not surprising, therefore, that while working with the automated system, researchers have discovered a new way to increase the number of blood vessels in the mini-organs to make them more like real kidneys. They also tried to expose the mini-organs to various substances and found that one of them, Fluvastatin, caused kidney damage in a mechanism that would now be investigated and could provide us with important clues about various kidney diseases.

References:

Czerniecki, Stefan M., et al. "High-Throughput Screening Enhances Kidney Organoid Differentiation from Human Pluripotent Stem Cells and Enables Automated Multidimensional Phenotyping." Cell stem cell 22.6 (2018): 929-940.

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