Cell lines hold promise for drugs, birds

For years, scientists have used mouse embryonic stem cells as a window to the mysteries of early development. In more recent times, the vast biomedical potential of human stem cells has sparked the public imagination and held out hope for millions of people with chronic cell-based diseases.

Now, scientists at UW–Madison have coaxed into existence a new line of cells from birds that could remake the poultry industry, provide new methods for manufacturing pharmaceuticals in the sterile encasement of the egg, and even help preserve endangered birds such as the California condor and whooping crane.

The cells, derived from fertilized bird eggs, are, for all practical purposes, the equivalent of avian stem cells. In culture, they appear to be immortal, showing an ability to remain in an undifferentiated state and reproduce indefinitely. The cells also can be persuaded to differentiate into cells representative of the four main types of tissues, muscle, nervous, connective and epithelial, which make up organs such as heart, skin, glands and reproductive structures.

“In avian species, embryonic development follows a slightly different path,” but these cultured embryonic cells seem to perform all the same feats that embryonic stem cells do in mammals, says Alice L. Wentworth, a UW–Madison scientist who, with her husband, animal science professor Bernard C. Wentworth, and colleagues Herng Tsai, Henry Hunt and Larry Bacon, was the first to isolate and culture the avian cells, known technically as blastodermal cells.

Like their human counterparts, the avian cell lines, which have been patented to the Wisconsin Alumni Research Foundation, have broad technological potential:

• For the poultry industry, frozen germ cell lines could pave the way for restoring quality genetic traits in fowl, a technology crucial to most forms of modern animal husbandry, but has heretofore been technically impossible in poultry.
• New methods for mass-producing pharmaceuticals could be developed using the egg as a sterile crucible for making valuable proteins and antibodies.
• Germ cell lines, derived from rare or endangered birds, could preserve their biological blueprints indefinitely in laboratory incubators and freezers. From these embryonic germ cells, diminished populations could be constantly replenished.
• Genetically altered fowl, harboring, for example, introduced genes for resistance to disease such as Newcastle’s disease, a devastating affliction of domesticated poultry, could have a significant economic impact and improve animal health.

The blastodermal cells are derived shortly after the fertilized egg is laid. At that stage, says Alice Wentworth, the egg consists of about 40,000 to 60,000 cells. Most of those cells, she says, will function to keep the embryo alive inside the shell, but among them are 400 or 500 cells that are truly embryonic in nature.

And among those few hundred embryonic cells are “primordial germ cells” that are destined to become the sperm and egg of the animal. In experiments, a “reporter gene” has been incorporated into these cultured cells, and these have been transferred into a recipient chicken embryo.

Subsequently, cells carrying the reporter gene have been found in the hatched chick as feathers, blood, muscle, connective tissue, epithelial and germ cells.

In other experiments with the Japanese quail, primordial germ cells have been used to create chimeras, Japanese quail that incorporated the transferred germ cells from another type of quail into their reproductive organs and carried these to the next generation.

“We have produced birds that are at least chimeras,” says Alice Wentworth. She notes that the acid test for a truly engineered bird would be for the chimeras to pass, through traditional breeding, to another generation the reporter or other genes carried in the cultured primordial germ cells. Those experiments, however, have yet to be done.

The ability to engineer chickens to mass produce valuable proteins or drugs in their eggs is an exciting potential technology, says Bernard Wentworth. “A hen lays 300 eggs a year. This technology is possible even if we’re unable to get the animal to pass the gene from generation to generation.”

Such technologies already exist in dairy cattle, for example, that have genes engineered into mammary cells so that the cows’ udders, in essence, become living bioreactors that produce valuable proteins.

The first likely application of the avian technology, according to Bernard Wentworth, will be the development of new reproductive technologies for domestic fowl and for preserving endangered species.

“Right now, we are not able to freeze avian semen,” he says. “However, these cell lines can be frozen, and this has a big potential impact for preserving endangered birds and for the poultry industry. That’s where this will be used first.”