San Diego Business Journal

Stem cell experts at the Burnham Institute say the recent findings that all federally approved embryonic stem cell lines are contaminated with a foreign molecule from mice, and thus, inadequate for human transplantation, justify the need for creating new cell lines, made possible by Proposition 71.

The need to develop new stem cell lines would boost the influence of the California Institute for Regenerative Medicine, a $3 billion initiative that California voters approved on the November ballot.

Scientists at the La Jolla-based Burnham Institute have taken the lead in creating new cell lines using nonfederal funds.

Moreover, they may have found a scientific process to get around the contamination problem, said Dr. John Reed, the president and chief executive officer of the Burnham Institute, and Dr. Evan Snyder, director of the research institute's stem cell research program.

"In a few months from now we will be able to confirm that we have a reliable and well-described method," Snyder said.

Snyder and Reed said scientists working in the field have long suspected that the federally approved lines were inadequate.

That suspicion has now been proven in a first study by scientists at the University of San Diego and the Salk Institute for Biological Studies in La Jolla, which found that if the stem cells are transplanted into humans, it could cause an immune reaction against the cells, which would wipe out their ability to deliver treatments for diseases such as diabetes, Alzheimer's or Parkinson's.

Snyder expects the findings, which were first published in the online edition of Nature Medicine on Jan. 23, are just the beginning of more contamination issues to be published in the coming months.

"Scientifically, the only way you can understand how cells become other kinds of cells is to be able to specify every molecule that's in your dish and, therapeutically, the only way you can effectively use them in patients is to also have them free of contamination from animal material or even human material," Snyder explained. "We think the cleanest way to do that is to not grow them on anything , but to have them completely self-contained."

Current available cells are grown in animal-derived products that could have contaminated them with viruses, pathogens or genes that are transferred to the cells and then do harm to people. Now, there's a first proof.

According to the study, all embryonic stem cells have picked up a type of a sialic acid called Neu5Gc during the culturing process.

When Neu5Gc enters the human body , by eating meat or drinking milk , the body's immune system recognizes the molecule as "alien" and rushes to make antibodies to attack it.

Scientists found this by exposing the stem cells to human blood serum that contained Neu5Gc antibodies. They concluded that it is likely that this would happen inside the human body too.

Snyder says the best way to get around the problem is to create entirely new cell lines, which is made possible by Proposition 71.

The initiative makes $295 million a year available over 10 years for California scientists to pursue that effort.

Reed sits on the 29-member committee that decides how to invest the money.
But the work is controversial, because the cells are derived from days-old human embryos that are destroyed. Many people say it is unethical.

President Bush has restricted federal funding to cell lines just derived before Aug. 9, 2001. Scientists have found that only about 20 of the more than 60 lines that existed worldwide proved usable.

But Snyder and Reed said there has been such significant scientific progress made since the 1990s, when these cell lines were derived, that just keeping them alive is challenging.

It may be too late to transfer the present lines to a new way of growing them. That doesn't mean that they are entirely unusable.

"There are other uses of stem cell lines rather than for therapies (namely research)," Snyder said. He noted that the Burnham Institute used the old cell lines to develop its new techniques.

Reed, however, said the federally approved cells would not meet the Food and Drug Administration's strict standards of human testing, let alone gain approval to be used for treating humans.

Both scientists said the California Institute for Regenerative Medicine's stem cell research measure is key to realize what is seen as the great potential. Because stem cells can grow into diverse tissue cells, including bone, muscle, brain and nerve tissue, scientists such as Snyder hope they will one day be used to repair damaged organs and treat major diseases. But that will take many years, given that stem cell research is still in its infancy.

Snyder said the Burnham Institute has about 700 embryos , donated by couples who no longer need them for in vitro fertilization , in its program that could be used to create new stem cell lines. This is a painstaking process.

"To establish a cell line can take six to 12 months, then you need to go through four to five months of splitting the cells, to ensure they grow can take another four months, and after you established that they grow, you still need to show that you can differentiate them," Snyder said. "Because of the low efficiency rate of generating lines, to make a single successful stem cell line can take 20 to 50 embryos."

A Harvard professor using old techniques required more than 300 embryos to make a dozen new stem cell lines, Snyder said.

That is why Proposition 71 is so important, he said.

"I think we should get started immediately so we can improve on the techniques and lines we have now," Snyder said.