Scientists at Boston Children’s Hospital, the Wyss Institute for Biologically Inspired Engineering at Harvard University and Boston University have developed a computer algorithm to test stem cells, a breakthrough that has allowed scientists to regrow part of a colon in a mouse.
In back to back papers published in the Aug. 14 issue of the journal “Cell,” scientists announced their breakthrough tool CellNet, a type of roadmap for cell and tissue engineering.
The tool allows scientists to analyze the network biology of a cell, or the genes that are turned on and off that give the cell certain characteristics.
Drawing from a library of public genome databases compiled through the algorithm, scientists can then compare the cell’s network to other cell types to more accurately pinpoint what a cell is or what it most closely resembles.
“Every cell that will be used in research or clinical application has to approach the identity of a particular tissue, the identity of a target cell. When people are interested in studying liver, and making a liver in a dish, they need to understand if the cells they have made function like a liver cell. And no one has had a comprehensive tool to do that,” said George Daley, the director of the Stem Cell Transplantation Program at Boston Children's and the senior investigator on both recently released studies. “We’ve had methods to examine the genes expressed, but it doesn’t give you a way to see how the cell functions.”
Until now. Using the device, scientists analyzed cells that had been converted from skin cells to liver cells.
“We were suspicious that that conversion was markedly incomplete … (and) we didn’t even detect liver characteristics in the cell,” Daley said. “…But when we looked under the hood, we saw it had a signature of the intestine. The intestine and liver come from the same embryonic source.”
The program allowed scientists to further tailor the cell to become more intestine-like. The cells were then transplanted into the colon of a mouse with inflammatory bowel disease, or Crohn’s disease.
“We took these converted cells and injected them into the mouse. And the mouse regrew its colon, which is pretty extraordinary,” Daley said.
Other scientists throughout the world are regrowing organs and tissues in mice as well, creating and changing stem cells into organ cells, which, when implanted, then replicate and self-organize into the desired organ.
But the device will allow scientists to more precisely analyze a cell, and then more accurately create stem cells or engineered cells.
The real world applications of the device are varied. Better cell understanding could have implications for creating patient-specific cells to assess drug responsiveness, for creating regenerative medicine, and for regrowing tissue or organs in patients, said James Collins, PhD, a core faculty member at the Wyss Institute, the William F. Warren Distinguished Professor at Boston University and co-senior investigator on one of the studies.
“We can assess how close the cell you’ve made is what you want it to be, and what else do you need to perturb to get it to the desired state,” Collins said
At Children’s, the device could have more immediate implications for how doctors use blood stem cells to treat cancers of the immune and blood system, already an active clinical trial at the hospital, or with development of cells to treat cystic fibrosis, retinal blindness, and neurodegenerative diseases.
“When we fast forward in 20 years, I think we will have a very different approach for treating disease,” Daley said. “We won’t throw our arms up to say we can’t treat heart failure, (only) with a whole transplant. We will be able to engraft tissues and restore function…we will be transplanting tissues and organoids… the future is this notion of turning cells into medicine.”
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