At first thought, it sounds like something straight from a science-fiction dystopian novel. Right now, while you read this, robots are creating thousands of miniature human kidneys out of stem cells.
In reality, however, it is a novel and exceptionally efficient way to boost biomedical research.
“This is a new ‘secret weapon’ in our fight against disease,” says one of the system’s designers, Benjamin Freeman from the University of Washington in the US.
In a paper published in the journal Cell Stem Cell, Freeman and a large group of collaborators describe a successful method for automating the creation of organoids – groups of cells that function like human organs.{%recommended 5864%}
The organoids are made from pluripotent stem cells, and are ideal for a form of computer-moderated testing known as high-throughput screening (HTS). This involves the rapid conduct of up to millions of genetic, pharmacological or chemical tests, and is a key technique for assessing the efficacy of potential medications.
Growing organoids using stem cells is a very recent development in medical research. Originally, the cells were cultured in two-dimensional sheets which, by definition, lacked the complex matrix of connections inherent in a three-dimensional shape.
The resulting models, therefore, were considered too simplistic and of limited value. Forming the cells into three-dimensional organoids allows much more coherent research, but poses major problems for mass production, requiring a lot of time and delicate human input.
The system created by Freeman and his colleagues employs liquid-handling robots. The machines place stem cells onto plates, each of which contains as many as 384 tiny wells. Over the course of 21 days, the robots coax the cells to link up and form miniature kidneys – with as many as 10 organoids per well and thus almost 4000 per plate.
“Ordinarily, just setting up an experiment of this magnitude would take a researcher all day, while the robot can do it in 20 minutes,” says Freedman.
“On top of that, the robot doesn’t get tired and make mistakes. There’s no question. For repetitive, tedious tasks like this, robots do a better job than humans.”
But the robots are far more than simply highly-engineered, super-fast lab technicians. They have also been trained to conduct an automated analysis of the organoids, called single cell RNA sequencing.
The approach is already producing surprises. The researchers report that although organoid kidneys do resemble the full-size organ, the robots also detected other types of cells within them that had not previously been noted.
The discovery allowed the scientists to quickly tweak the culturing process to produce more accurate models.
“These findings give us a better idea of the nature of these organoids and provide a baseline from which we can make improvements,” explains Freedman.
“The value of this high-throughput platform is that we can now alter our procedure at any point, in many different ways, and quickly see which of these changes produces a better result.”
