As the idea of growing tiny human organs in lab dishes has moved in recent years from futuristic science fiction to actual bioscientific reality, the usefulness of organoids as a research tool for studying the digestive system swiftly encountered a bottleneck — these valuable tissues are quite difficult to make.

Even with highly trained teams using all the best ingredients and equipment, one batch of starting material can generate lots of tiny spheroids of organ precursor cells that can then be grown into specific organoid types. But the next batch may produce few spheroids or none at all.

As a result, lab teams often experience delays making the organoids they need for pre-clinical experiments that seek to test the safety or potency of potential medications or for basic research to delve deeper into the genetic and molecular activities that cause disease.

Now, in a paper published June 28, 2022, in Stem Cell Reports, a team of experts at Cincinnati Children’s reports developing a method that overcomes this production bottleneck. The new method already is being used to advance organoid studies within the medical center. But since the materials involved can be frozen and thawed and still produce high-quality organoids, this discovery makes it possible to ship starter materials to other labs anywhere in the world — which could spark dramatically accelerated use of human gastrointestinal organoids throughout medical research.

“This method can make organoids a more accessible tool,” says first author Amy Pitstick, MS, manager of the Pluripotent Stem Cell Facility at Cincinnati Children’s. “We show that the aggregation approach consistently produces high yields and we have proven that precursor cells can be thawed from cyrogenic storage to produce organoids of the small intestine.”

“Using this approach will make it possible for many research labs to use organoids in their experiments without the time and expense of learning how to grow induced pluripotent stem cells (iPSCs),” says corresponding author Chris Mayhew, PhD, director of the Pluripotent Stem Cell Facility. “The ability to freeze the precursor cells also will allow labs to easily make organoids without having to start each new experiment with complicated and highly variable iPSC differentiation.”

About the new process

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