Stem cells isolated from monkey eggs continue producing variety of other cells

Wake Forest University Baptist Medical Center investigators report

A line of monkey stem cells, produced without the use of an embryo, has reproduced for more than two years and still retains the capability of differentiating into a variety of tissue types, a research team reports in the current on-line edition of the Proceedings of the National Academy of Sciences.

Kent Vrana, Ph.D., professor of physiology and pharmacology at Wake Forest University Baptist Medical Center and the first author on the report, said the stem cells have produced two types of neurons, and many other tissues such as heart, smooth muscle and beating cilia, the tiny hairlike extensions that line the airways.

The research team, from four universities and two private companies, first reported the stem cell line in January 2002 in the journal Science. At that time, some other scientists thought that the stem cell line might stop after several generations.

Vrana reports in the current paper that the stem cells possess the biological properties of indefinite replication found in cancer cells and embryonic stem cells.

These stem cells were developed by a process called parthenogenesis — using only an egg from a female monkey and no sperm. The resulting multiplying group of cells, called a parthenote, cannot successfully implant into the mother’s womb and hence cannot develop any further than what is called the blastocyst stage, essentially a ball of cells.

But the team was able to take cells from that blastocyst and begin the stem cell line, called Cyno-1. Jason Hipp, a Wake Forest graduate student and second author on the paper, said this approach could “bypass the need for creating a competent embryo for the creation of stem cells.”

Of great interest is the potential for developing an unlimited number of one type of neuron. These neurons could eventually pave the way for the treatment of Parkinson’s disease.

The neurons synthesize a neurotransmitter called dopamine, and are impaired in people with Parkinson’s disease.

“Clinical transplantation of specific fetal neurons has shown promise in the treatment of Parkinson’s and Huntington’s disease,” said Vrana, “but obtaining such cells from animals or human fetal brain remains problematic.” Obtaining cells produced in the laboratory from stem cells that come from parthenotes “could alleviate some of the ethical and technical concerns of human cell therapy.”

Vrana said the striking ability of these stem cells derived from parthenotes to differentiate suggest a valid alternative to stem cells derived from normal fertilization.

To test whether the stem cells were “pluripotent” — able to produce any cells — the stem cells were injected into a mouse without a functioning immune system. The cells produced all three of the body’s cell layers: ectoderm (neuron, skin and hair follicles), mesoderm (cartilage, muscle and bone) and endoderm (intestinal epithelia), according to Jose Cibelli, professor of animal science at Michigan State University and co-author.

Moreover, the monkey stem cells have a normal number of chromosomes, Vrana said.

Parthenogenesis is not new biologically, but it is unknown in mammals. “Flies, ants, lizards, snakes, birds, reptiles, amphibians, honeybees and crayfish routinely reproduce in this manner. Placental mammals are not capable of this form of reproduction,” said Vrana.

Among other members of the team were Ashley Goss, undergraduate student, Kathleen A. Grant, Ph.D., professor, Brian A. McCool, Ph.D., and Stephen J. Walker, Ph.D., assistant professors of physiology and pharmacology, and David Riddle, Ph.D., assistant professor of neurobiology and anatomy, all from Wake Forest; Peter Wettstein from the Department of Microbiology and Immunology at the Mayo Clinic; Lorenz Studer and Viviane Tabor from the Sloan Kettering Cancer Center in New York; Kerrianne Cunniff from Millennium Pharmaceuticals in Cambridge, Mass.; and Michael D. West and other researchers from Advanced Cell Technology in Worcester, Mass.

Additional Contact: Karen Richardson (rchrdsn@wfubmc.edu) at (336) 716-4587