"Most attempts to directly convert one specialized cell type to another have depended on a trial and error approach," notes Cahan, principle architect of CellNet and a post-doctoral scientist in the Daley lab. "Until now, quality control metrics for engineered cells have not gotten to the core defining features of a cell type."
In both test cases, CellNet showed that the engineered cells hadn't completely converted, retaining some characteristics of their cells of origin—but pointed to specific genetic tweaks that could be done in the lab to fix the problem.
CellNet also pointed out some useful properties that weren't apparent before. "We found that liver-like cells made from mouse skin were actually more like intestinal cells," says Morris. "In fact, the converted skin cells could engraft into mice with inflammatory bowel disease—Crohn's or ulcerative colitis. After a short time, the cells became highly similar to native colon cells and assisted healing of the damaged tissue, a finding that surprised and excited us."
Guidance for stem cell engineering
Together, the two studies establish some general principles for stem cell science:
1) The GRN of iPS cells created by reprogramming a mature cell is nearly identical to that of stem cells made from embryos, confirming that iPS cells are a good raw material for creating specialized cells.
2) Once engineered cells are engrafted into laboratory mice, their GRN becomes even closer to that of the true target tissue, indicating that the body's own tissues contribute signals to enhance the performance of transplanted cells.
3) Differentiating pluripotent stem cells into specific tissues is currently more effective than attempting to convert one specialized cell directly to another, creating cells whose GRNs are much like those of cells in the body.
4) Most specialized cells made from other specialized cells retain some "memory" of th
|SOURCE Boston Children's Hospital|
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