DNA errors could make lab-made stem cells fail, scientists say

PHILADELPHIA, May 10 (UPI) — Induced pluripotent stem cells have allowed scientists to grow mini-organs with the potential to model diseases, test treatments and possibly lead to the growth of whole organs matched to patient’s bodies.

New research at the University of Pennsylvania suggests the cells could fail because of shifts in how DNA folds inside a cell’s nucleus, preventing it from differentiating properly into the type of adult cell intended.

IPSCs are cells taken from a person’s body, often the skin, and induced in the lab to return to their undifferentiated form as stem cells. These cells are then motivated to become the type of cell scientists need for tissues they are growing.

The lab-made stem cells have been used in studies conducted in the last several months alone for targeted cancer treatments, grow functional heart muscle and lab-grown skin for burn victims, among many others.

Researchers in the new study suggest the process of turning cells into IPSCs changes the way DNA folds and retains some of the folds associated with their previous type, which may also affect the way DNA is expressed and cause other issues.

“We know there is a link between the topology of the genome and gene expression,” Jennifer Phillips-Cremins, an assistant professor at the school of engineering and and applied science at the University of Pennsylvania, said in a press release. “So this motivated us to explore how the genetic material is reconfigured in three dimensions inside the nucleus during the reprogramming of mature brain cells to pluripotency. We found evidence for sophisticated configurations that differ in important ways between iPS cells and embryonic stem cells.”

In the study, published in Cell: Stem Cell, the researchers used fine-resolution architecture maps to find epigenetic markers associated with gene expression in embryonic stem cells, neural progenitor cells and induced pluripotent stem cells derived from NPCs and compare differences in genes reconnecting to the proper targets during cell reprogramming.

They found some IPSCs do not reconnect properly, and suggest better methods — possibly using information from their maps and others — to reconnect DNA in cells could improve their outcome and use in the lab.

“We found marked differences among the heatmaps we generated for each cell type,” said Jonathan Beagan, a graduate student at the University of Pennsylvania. “Our observations are important because they suggest that, if we can push the 3D genome conformation of cells that we are turning into IPSCs to be closer to that of embryonic stem cells, then we can possibly generate IPSCs that match gold-standard pluripotent stem cells more rapidly and efficiently.”