The differences in gene expression could be problematic, Lowry said, because some of these same differentially expressed genes in the progeny are genes that are expressed during cancer development. Also worrisome was their developmental maturity would they work correctly when transplanted into humans? As part of their study, the team left the differentiating cells in culture about a month longer to see if they would further mature, and there was some modest but statistically significant maturation. However, genetic discrepancies remained.
These discrepancies could be critical, Patterson said, particularly in the hepatocytes. During fetal development, these cells express proteins that aid the metabolism of the fetus, a role they don't play later in adults.
"The roles these cells play in the fetus and the adult are inherently different," she said. "It may be that the progeny, if transplanted into a human, would mature to the same levels as those found in the adult liver. We don't know."
The team then compared the progeny to cells from humans that were closer to the progeny's developmental maturity and found that the two types of cells were indeed becoming more similar in gene expression and functionality, Lowry said.
The UCLA team is not the first to suggest that the progeny of human pluripotent stem cells reflect an early developmental immaturity. However, these data put a more precise window on their developmental age.
Going forward, Lowry and his team are going to study the 100 genes being differentially expressed in the progeny to see if manipulating some or all of them results in the maturation of the cells.
"These findings provide support for the idea that human pluripotent stem cells can serve as useful in vitro models of early human development, but also raise important issues for disease modeling and the clinical applications of their derivatives," the study states.
|Contact: Kim Irwin|
University of California - Los Angeles Health Sciences