The paradox of single motherhood is that to become a single mother requires in the first instance a father.
True unisexual reproduction involves the process of parthenogenesis, in which the female reproduces its kind without fecundation by the male. In fact, parthenogenesis derives from the Greek word parthenos, meaning “virgin.”
“The parthenogenetic process,” observed embryologist Jos Cibelli, leads to stem cells without creating embryos that normally require an egg from the mother and a sperm from the father. Embryonic development is initiated directly from an unfertilized egg.”
Cibelli, vice president of research at Advanced Cell Technology Inc. (ACT) in Worcester, Mass., is lead author of a paper in today’s Science, dated Feb. 1, 2002. Its title: “Parthenogenetic stem cells in nonhuman primates.” Its senior author is cell biologist Michael West, president and CEO of ACT.
“We report here a cell line that will give rise to pretty much any cell type in your body,” Cibelli told BioWorld Today. “The remarkable part of it,” he added, “is that it doesn’t have any male contribution. All of the cells were derived from female chromosomes. This is the first time you can have such a plastic cell type, or cell line, coming from the female donor that is still alive.
“The beauty of it is,” Cibelli continued, “that this cynomolgus monkey that gave us the cell line is a normal macaque [Macaca fascicularis] in the primate colony at Wake Forest University School of Medicine in Winston-Salem, N.C. She’s still alive, and produces unique cell types, including dopaminergic neurons the most remarkable ones. What is novel in this finding of ours,” he went on, “is that for the first time you have a primate stem cell that can be considered autologous self’ produced from the same animal.”
That donor female monkey’s handler is co-author Kathleen Grant, a behavioral pharmacologist at Wake Forest. “My area of research,” she observed, “is to develop animal models of alcohol abuse and alcoholism. But this donor herself, who’s about 7 years old, is not currently, nor ever in the past has been, in an alcohol protocol.”
Subhuman Primates Now, Human Patients Later
“There’s nothing unique about the monkeys themselves,” Cibelli said, “except that we had access to them. So it was a source for us, a way of proving the principle in a primate before we move into humans.”
So far, of Wake Forest’s very large primate colony, the co-authors have engaged the services of only that one donor female. “To begin with,” Cibelli recounted, “by a surgical procedure, we collected 77 of her eggs from a superovulating ovary then narrowed those starter numbers from 28 to two and eventually to that single ovum. Everything else was done in vitro genetic activation of the eggs, then developing the cell line from one of them.
“In vitro we produced a cell line from that one egg,” Cibelli related. “And when we cultured that cell line in a particular way, it continued to divide indefinitely for 10 months. So it was an unlimited source of that cell type. However, as soon as we changed the culture conditions, that cell line began to produce a spectrum of cell types. The in vitro differentiation that we were able to obtain from them was smooth muscle, spontaneously beating cardiac muscle, ciliated epithelia, fat cells and dopamine-secreting neurons. That was the most remarkable one of all. Up to 25 percent of dopaminergic differentiation was reported in the Science paper. However, since we submitted the paper until now, dopamine differentiation has gone up to 40 percent.
“Then we injected the cell line into a SCID mouse, which doesn’t have any immune system. At that point, the cells basically went wild. The tissues that we obtained in vivo from that mouse included whole, very complex structures, such as hair follicles with their sebaceous glands, bone, cartilage, intestinal epithelia, ganglia, skin. So there’s a number of different tissues that were pretty much derivative from the three embryonic germ layers ectoderm, mesoderm and endoderm.”
Cibelli went on: “One way to induce rapid cell differentiation is to take the cells and put them in a completely foreign environment called a teratoma a benign tumor. It’s a massive growth that’s foreign to the individual you put it into. In this Science paper, we put these stem cells derived from our monkey donor female into the SCID mouse, and they predictably divided rapidly into many different cell types. The whole teratoma cluster consisted of the progeny cells.”
Grant picked up the story: “So we took that ball of cells, which very much resembled a tumor, and when we sorted through them we could find many different cell types. That reflects their pluripotential capacity, and really demonstrates that our stem cells are indeed functioning as an embryonic stem cell line, in all three germ layers.”
In Cross-Hairs: Dopamine To Treat Parkinson’s
Cibelli pointed out, “The differentiation in vivo was completely random. In vitro, part of it was actually targeted, sort of induced. All the studies on targeting dopaminergic neurons pretty much use standard protocol. We’re planning on doing all those experiments with these cell lines on the Parkinson’s disease animal models in rats and monkeys. So this will be the first step to show that these parthenogenetic cells can be clinically functional, in vitro and in vivo. That’s what we’re doing now.
“We have to proceed carefully,” he noted, “but I hope that as soon as we can repeat this protocol of parthenogenesis with human eggs, I would say that four or five years after that, we’ll be able to put them into human Parkinson’s patients. In the meantime we will be definitely trying to use the same human cells. Let’s say six months from now we get parthenogenetic cell lines from a human egg. We would have to do all the animal studies first during that time.
’Meanwhile, the next step ongoing right now will be to take the cells, put them back into our donor female monkey, and determine whether or not there will be any immunological rejection from her by other primates. That will determine if these cells are being recognized as self or as foreign tissue.”