Stem Cell RESEARCH is a controversial topic. Some people argue that stem cell research is the beginning of a slippery slope to reproductive cloning, whereas proponents, including medical researchers, state that stem cell research is essential and has the potential for significant medical benefit. In light of this controversy, on August 9, 2001, U.S. President George W. Bush announced that federal taxpayer funding for human embryonic stem cell research would be limited to research using stem cells lines that are currently in existence.
Research has been ongoing for many years to circumvent the ethical issues surrounding research on human embryonic stem cells. Researchers have been developing techniques of isolating stem cells that are as universal and potent as human embryonic stem cells but that do not involve human embryos. The potential benefit of using embryonic stem cells holds great promise for the field of medicine, including potential therapies or even cures for Parkinson’s disease, multiple sclerosis, cardiac disease, and spinal cord injuries.
One way to circumvent the ethical dilemma of using human embryos is to use stem cells from non-human primates. There are some unique advantages and disadvantages of using cells from nonhuman primates, such as rhesus and cynomolgus monkeys. One potential advantage of these primates is that they have a very close genetic relationship to human beings, which allows more clinically relevant research to be conducted. Researchers have estimated the genetic similarity between some non-human primates and humans to be greater than 98.5 percent. This is particularly important in neural degenerative disease applications. In these applications, the mouse is inadequate as a transplantation or disease model because of the genetic variability between humans and mice.
In addition, National Institutes of Health funding can currently be obtained to make unlimited stem cell lines from nonhuman primates, as opposed to using human embryonic stem cells.
Also, because these primates have been studied extensively over the years, many disease models of these primates exist. Experimentation with nonhuman primates’ embryonic stem cells is an important prerequisite to beginning to use human embryonic cells, especially because of ethical and moral considerations. The major disadvantage is that these cells ultimately are not human and are therefore unlikely to be used in clinical transplant programs.
cloning
The majority of cloning studies published to date have been in mice, using a technique called somatic cell nuclear transfer. This involves transplanting the nucleus containing an individual’s DNA to an egg cell that has had its genetic material removed. This technique of somatic cell nuclear transfer has worked fairly well in mice but has not historically produced satisfactory results in primates.
However, researchers at the Health & Science University in Portland, Oregon, in November 2007 were able to isolate nonhuman primate embryonic stem cells and clone them. Being able to isolate embryonic stem cells and successfully clone them is an important milestone for two important reasons. First, embryonic stem cells harvested from in vitro fertilization (IVF) are not genetically identical to the host, whereas embryonic stem cells isolated and cloned from a particular host are genetically identical, which is a benefit when infusing them back into the same host. Any infusion of the IVF-obtained stem cells back to a host would undoubtedly result in rejection without continuous application of an immunosuppressive drug, which in and of itself is fraught with adverse effects. Second, being able to isolate embryonic stem cells from primates circumvents the ethical issues regarding the use of human embryonic stem cells.
Researchers led by Dr. Shoukhrat Mitalipov took nuclei from skin cells of an adult monkey and implanted them into cells of an egg from a fertile monkey after the nucleus had been removed. They then stimulated the cells into forming a round and hollow formation of cells—a type of immature embryo called a blastocyst. Extracting the inner-most cells, the researchers were able to create two embryonic stem cell lines identical to the host.
The genetic similarity between some nonhuman primates and humans may be greater than 98.5 percent.
therapeutic cloning versus reproductive cloning
This type of work is known as therapeutic cloning. Therapeutic cloning should be distinguished from reproductive cloning. As opposed to reproductive cloning, therapeutic cloning involves extracting stem cells to fuse with an egg, and after maturation, the blastocyst can be induced to form a tissue that is desired by the researcher. If therapeutic cloning is continued and induced, then it can potentially involve reproductive cloning, which has been performed on sheep, but not yet on monkeys. Although theoretically it is possible to use somatic cell nuclear transfer to clone—so-called reproductive cloning—the process is extremely difficult. In fact, Dolly the sheep, the first cloned animal, was born via reproductive cloning only after experimenting with 277 eggs.
LIMITATIONS AND UPCOMING ADVANCES
It is important to note that there are many limitations to overcome when working with nonhu-man primate embryonic stem cells. The primate cell lines used for research are more cumbersome with regard to their requirements for growth. They require considerably more technical expertise and attention when compared with the mouse growth requirement. Another limitation with primate embryonic stem cells is that they can sometimes spontaneously differentiate. This causes the cloning efficiency of the differentiated cells to be less than one percent in some cases.
According to Wolf, et al., much more work has to be done in the field of primate embryonic stem cell research before effective application is undertaken. At present, very little is known regarding the differences among various cell lines. Better understanding would make it more feasible to establish stem cell lines to derive a primate line with more simplified growth medium and, in effect, use methods that would make the lines replicate faster. This is because at present, the variability among various stem cell lines is unknown; therefore, investigators from different centers working on different cell lines may not be able to compare results.
It is critical to start large numbers of embryonic stem cell lines to more completely characterize these lines as a resource for the scientific community. This way, scientific research in the field of nonhuman primate embryonic stem cells can progress so that potential medical benefits, including cures for ailments such as Parkinson’s disease and multiple sclerosis, can be pursued.
