Researchers in Seattle have taken advantage of two of the hottest trends in biotech – cell reprogramming and CRISPR/Cas9 gene editing – to create human stem cells that glow as they turn into different tissue types.
The Allen Institute for Cell Science is making the genetically modified cells available to researchers around the world, with the aim of unlocking the secrets behind cell development.
“These are the first five cell lines in a collection of about 20 that we hope to be releasing in the next year,” Susanne Rafelski, the institute’s director of assay development, told GeekWire in advance of today’s unveiling of the Allen Cell Collection.
The institute’s executive director, Rick Horwitz, explained that each of the millions of cells in our body is like a city, with resources that move around from where they’re made to where they’re used.
“With these cell lines, we aim to give the cell science community a kind of live traffic map, to see when and where the parts of the cell are with the clarity and consistency they need to make progress toward understanding human health and tackling disease,” he said in a news release.
Ruwanthi Gunawardane, the institute’s director of stem cells and gene editing, said the cells are particularly valuable because they can turn into a wide range of tissue types, such as beating heart cells, active neurons, or kidney or liver cells.
“We think this can be a hypothesis generator for the research community,” she said.
The process began with healthy, normal skin cells that were donated by an anonymous Asian male. Those cells were reprogrammed to become what are known as induced pluripotent stem cells, or IPS ceiis. Like embryonic stem cells, IPS cells are capable of developing into multiple tissue types.
The Allen Institute’s researchers took those garden-variety IPS cells, and used the CRISPR/Cas9 gene-editing technique to insert fluorescent protein tags at spots in the cells’ genetic code that are associated with specific cellular structures.
The first five structures to be targeted have to do with the cells’ nucleus, mitochondria, microtubules, cell-to-cell junctions and adhesions. When the tagged cells are monitored under a microscope, the fluorescent structures stand out in specific wavelengths.
“The images and movies we can generate from these lines show the cell’s major structures with astonishing clarity, and empower a broad, multistructure view of how cells change as they execute their varous activities and turn into different kinds of cells,” Rafelski said.
The cell lines already are being used by researchers at the University of Washington and elsewhere to study how stem cells differentiate themselves into heart cells, and how mutations can lead to heart disease, Gunawardane said.
Other potential applications include screening drugs for safety and efficacy, and studying how diseased cells differ from normal cells. The color-coded stem cells could help researchers develop more personalized treatments for diseases and even smooth the way for tissue regeneration.
“It’s going to be the watching, the direct observation in live cells of the process of differentiation that will be a very cool game changer for the community,” Rafelski said. “To understand why cells are what they are, and how they turn from one cell into another.”
Gunawardane said each cell line took about six months to develop. That covers the time required for the CRISPR process as well as cloning the cells and doing rigorous quality control. The cell lines are being distributed through the Coriell Institute for Medical Research at a cost of $600 per vial.
“There are a couple of gene-edited lines out there, similar to what we’ve done, and they run in the range of several thousand dollars,” she said. “The cost of $600 pretty much just covers the distribution cost.”
That’s in line with the mission of the Allen Institute for Cell Science, which was founded two years ago with a $100 million funding commitment from Microsoft co-founder Paul Allen. In all of his scientific initiatives – which range from neuroscience to artificial intelligence – Allen has aimed to foster public access to the fruits of research.
Update for 7:15 p.m. PT Dec. 1: University of Washington medical researchers Charles Murry and Michael Regnier emailed further details about how they’re using the stem cells in their study of heart cells. Here’s how Regnier explained their work:
“The Allen Cell Collection will provide a great new resource to scientists studying a variety of questions in cell biology. They have produced human pluripotent stem cells that express proteins linked with fluorescent molecules for a variety of cell structures, so that the development of these structures and their roles in cell function can be studied over time.
“We will turn these stem cells into human heart muscle cells and use high-resolution imaging techniques to study the development of organelles called myofibrils that are responsible for rhythmic beating of the heart. We will first study the role of microtubules in the development of myofibril structure. This may provide important new clues into how these contracting organelles form correctly during heart development.
“We will then study how heart muscle cells respond to chemical and mechanical stimuli that make them grow and add new myofibrils. Our long-term goal is to determine how mutations in proteins that are associated with heart disease alter the development of myofibrils and the beating properties of heart muscle cells.”
Murry said the research could show why heart muscle cells “stop dividing and fail to re-enter the cell cycle after injury like myocardial infarction” – that is, a heart attack.