Breakthrough could help treat degenerative diseases

Three new lines of human embryonic stem cells (hESCs) that were the first in the world to be produced without contamination from any animal – mice or cow – components and according to Good Manufacturing Practices (GMP) conditions have been announced by Hadassah University Medical Center researchers after 12 years of work.

Cell lines could eventually be used to provide infinite numbers that differentiate into many types of human tissue and are aimed eventually to repair a wide range of diseases, noted Prof. Benjamin Reubinoff, a world-renowned stem-cell pioneer and the new chairman of obstetrics/gynecology at the Ein Kerem medical center. He reported his and his colleagues’ breakthrough in the latest issue of the open-access Public Library of Science journal PLoS One, in an article titled: “Derivation of Xeno- Free and GMP-Grade Human Embryonic Stem Cells – Platforms for Future Clinical Applications.”

The lines were produced at Hadassah – which has the only GMP hospital lab of its kind in Israel – from six-day- old embryos donated by couples who had completed in-vitro fertilization treatments.

“No one else managed to accomplish what we did before, because it was very difficult work to translate such know-how from the research lab into a system suitable for implantation into man,” Reubinoff – the longtime director of the on-campus Sidney and Judy Swartz Human Embryonic Stem Cell Research Center – told The Jerusalem Post on Monday.

While the lines of new stem cells would be provided at nominal fees to academic research centers around the world, they would be sold to commercial companies by Hadassah, which has put the new cell lines in locked freezers.

Embryonic stem cells can differentiate and mature into any cell type in the human body, which gives them the potential to serve as an infinite source of regenerative cells for transplantation in severe degenerative diseases such as agerelated macular degeneration (AMD), type 1 diabetes, heart failure and Parkinson’s.

Most cell lines produced throughout the world are suitable for basic scientific research but far from ideal for transplantation, Reubinoff said.

During the Republican Bush administration, large amounts of federal funds were denied to human embryonic stem cell research because of right-wing opposition to their production from embryos not used for infertility treatment; this use was claimed by some as “murder.”

But as Jewish law does not regard the use of unused embryos as taking a life since each is only an unimplanted potential life, Israeli stem cell research surged forward, much of it thanks to Reubinoff and his colleagues.

After reviewing the ethical procedures involved in the embryo donation and the production of the stem cells, the Health Ministry’s supreme Helsinki Committee on Human Medical Experimentation gave the goahead, while the US National Institutes of Health found them appropriate and granted their approval after the work was done. Stating that they were produced in an ethical way, the federal government enables US researchers to use such new cell lines in studies that the government funds.

The new Hadassah cell lines have already been provided to two Israeli companies – Cell Cure Neurosciences Ltd.

and Kadimastem Ltd. – which are using them for the development of transplantation treatments; Cell Cure for “dry” AMD and Kadimastem for type 1 diabetes. Hadassah’s technology transfer company Hadasit awarded licenses to the two companies and is overseeing the process.

“Until now, hESCs were produced mostly using feeder cells from mice and albumen from cows. This is not good because it may cause contamination of the human cells with animalderived viruses,” said Reubinoff.

“Our cell lines are free of all that.”

The first patients to undergo hESC implantation in clinical trials are expected to be those suffering from the ophthalmological disease, which is a very common cause of blindness in older people. At present, there are no treatments to halt such patients’ deterioration of vision and certainly no cures.

Reubinoff said that those who use Hadassah stem cell lines will be able to follow the team’s guidelines. “Safety is always the end point,” he said. “This is a platform for treating other diseases.

After trials for AMD, I think clinical trials for multiple sclerosis and other neurological disorders will be in the next wave.”