A map app to track stem cells
By Alison Gillespie, National Institute of Standards and Technology
Researchers who work with stem cells have ambitious goals. Some want to cure cancer or treat heart disease. Others want to grow the tissues and organs that patients need for transplants. Some groups are even working to develop highly personalized medicines, tailored to an individual’s genetics. All of these ideas face a similar hurdle, however: The development of measurement tools for stem cell production is challenging, making it hard to determine what makes various new stem cell-related products safe, effective or high-quality.
Over the last few years, NIST scientists have been trying to solve this problem in a way that will seem familiar to anyone who has ever used a smart phone and a mapping application. The system they have developed, however, goes way beyond anything found in a typical app. It combines video footage and high-power computation to bring the world one step closer to evaluating, understanding and quantifying features of cell populations that could be used in related therapies or products.
The new image analysis system, called Web Image Processing Pipeline (WIPP), is like a mapping app that allows a user to interact with microscopic views of macroscopic objects. With WIPP, a cell culture is divided into real locations that can be explored and referenced with a system very much like GPS points or the quadrants on a geographic map or mapping app. But WIPP also allows a user to examine what’s happening in a petri dish over time, from any point of view they choose.
The work on this new interface is detailed in a new reference book, Web Microanalysis of Big Image Data(link is external), published in January 2018 by Springer Verlag. It was also described in an article published in the journal Stem Cell Research in May 2016(link is external).
“You can share results with colleagues and analyze what’s happening with these cells in many different ways—in space, over time and by their function. And you can review how the cell changes in time, over and over again,” said Peter Bajcsy, author of the book and the IT lead for the research behind WIPP.
WIPP was designed for work with induced pluripotent stem (iPS) cells, which are cells taken from the tissue of an adult and processed to behave like an embryonic stem cell. iPS cells can be used to make new cells from all three of the basic human body layers: ectoderm (skin), endoderm (gastrointestinal and respiratory tracts), and mesoderm (blood and bone). iPS cell technologies are still relatively new, and it is unclear which tissue types derived from iPS cells will have the greatest impact first. Researchers are seeking ways to effectively and reliably measure progress as cells become different cell types during processing.
Model iPS lines are usually purchased from established cell banks, which operate somewhat like blood banks. Depending on the application and the laboratory in which they are grown, the cells are cultured in different specialized media and on different specially treated surfaces. The media are replenished on a regular basis to keep the living cells in a pluripotent state as they expand in number. They can be used in experiments to study fundamental biology, or they can be differentiated into specific mature cells that can be developed for medical treatments or used to test drugs.
Every cell matters. If one undesirable cell reproduces rapidly and comes to dominate the culture, it could become a tumor or make the preparation otherwise unsuitable for use as a therapy. To fully understand what’s happening in these stem cell systems, a researcher would want to know the characteristics of the cells in the dish by watching them change, grow, reproduce or die in order to eliminate as many of the potential dangers for patients as possible.
“We believe live cell imaging is really the only tool you can use to follow single cells in time and understand at the single cell level how behavior at a given point in time is related to the future,” says Michael Halter, team leader for image acquisition for the WIPP project. “We don’t just want to analyze one colony or a few colonies. We want to look at all of the colonies and we want to look at them over time.”