BioWorld International Correspondent
LONDON - An embryonic stem cell line with the mutation for cystic fibrosis has been developed at King's College London, opening the way for a new approach to treatments for the inherited lung disease.
It is the first human embryonic stem cell line to carry a mutation for an inherited disorder, and it was derived from a 3-day-old embryo screened by pre-implantation genetic diagnosis.
The cell line was produced at the Stem Cell Laboratory at King's, where two other embryonic stem cell lines have been developed. Speaking at the British Association's annual meeting in Exeter last week, the laboratory director, Stephen Minger, said the CF cell lines would be used to study how the mutation affects cell function, to screen for new drugs and to research gene therapies.
"As the animal models of cystic fibrosis don't fully repeat all aspects of the disease, having a human cell line with this genetic defect will be very useful," he said. He hopes to team with CF researchers to exploit the potential of the cells.
In order to justify the use of embryos produced by in vitro fertilization to derive stem cell lines, researchers have placed most emphasis on their potential in cell-replacement therapy. However, Minger said that initially the technology would be more important in research in inherited diseases. He is attempting to derive additional embryonic stem cell lines encoding single-gene disorders.
The stem cells with the CF mutation appear normal, but Minger's team is trying to make them differentiate into epithelial cells, at which point they believe the mutation will be expressed.
Minger's group also is using fetal stem cells to develop cell lines. They have succeeded in generating neuron cell lines from brain stem cells, but they cannot be sustained. "We hope to get around this - we think that when [the stem cells] are taken out of the brain, they are already running a program."
In addition, two hepatocyte cell lines have been established from stem cells from developing fetal liver, which to date have expanded for six months.
"We have also started to grow retinal stem cells and are trying to isolate photoreceptors and to expand the progenitor cells," Minger said, adding that they have been growing for a month now. "So although the developing [fetal] brain may not provide us with sustainable cells, other organs may."
Another researcher described how fetal stem cells might be used as autologous transplants to repair the brain damage that occurs commonly in premature babies. Huseyin Mehmet, of the faculty of medicine at Imperial College London, isolated stem cells from the blood and bone marrow of fetuses at 15-16 weeks gestation.
When injected into the brains of mice in utero, those cells integrated into the tissue and were detected when the mice were delivered normally at term.
"Now we need to show if these brain implants are functional and can correct brain damage [in mice]," Mehmet said. "The dream is that when a baby is born prematurely, we have already got an [autologous] stem cell bank for cell-replacement therapy."
Brain damage in premature infants is growing, as more and more babies are able to survive prematurity. Babies born before 30 weeks gestation have an 80 percent chance of some kind of neurological deficit, and the earlier they are born, the greater the risk.
Mehmet's work to date has used fetuses from elective terminations, but he has identified a gene that is linked to prematurity, and he believes it will be possible to detect women at risk of having premature babies and extract stem cells early in a pregnancy.