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Stem Cell Breakthrough

By Sean Henahan, Access Excellence

Washington, DC (11/05/98)- After nearly 20 years of research, the long sought grail of culturing human stem cells has been achieved by two separate research groups. The breakthrough has implications for everything from basic developmental biology to organ transplantation, and raises numerous bioethical questions.

Embryonic stem-cells can develop into any form of cell in the human body. They have a number of impressive characteristics, including the ability to proliferate indefinitely. Researchers have been stymied over the years by two aspects of stem cells- they are difficult to find and even more difficult to culture.

A research team at the University of Wisconsin-Madison solved both problems. They utilized human blastocysts (embryos less than one week old), donated with permission of patients participating in a fertility program, as the source for the stem-cells. The blastocyst is the stage of development at which the embryo's inner cell mass forms. For a very short time, this inner cell mass harbors embryonic stem cells. After the cells are extracted, they are placed in a special culture medium.The culture medium, a proprietary preparation, provided the cells with everything they needed to proliferate.

"This research shows you can derive and culture these cells, and it opens the possibility for some dramatic new transplantation therapies. Although a great deal of basic research needs to be done before these cells can lead to human therapies, I believe that in the long run they will revolutionize many aspects of transplantation medicine," said developmental biologist James A. Thomson, University of Wisconsin.

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The Wisconsin team was able to establish five independent cell lines in culture, and to grow them indefinitely. The cells differentiated into the three primary germ lines that make up the body - endoderm, ectoderm and mesoderm - and subsequently into arrays of tissue cells such as cartilage, bone, muscle, neural and gut cells. So far, this process of cell differentiation is random and cannot be guided by the scientists.

The next step will be to determine methods to direct the human embryonic stem cells to become specific types of cells. Accomplishing this would allow the production of virtually unlimited amounts of any cell type. This could lead to new approaches for the treatment of heart disease, Parkinson's disease and many types of cancer.

Another Approach from Johns Hopkins

Researchers from Johns Hopkins University reported that they too had managed to culture human stem-cells using an entirely different approach. The researchers searched small samples of non-living, human fetal tissue to find primordial germ cells, (PGC) the cells that eventually would have become eggs and sperm. The single PGCs were placed on a "feeder layer" of mouse connective tissue cells, surrounded by a broth of nutrients and highly specialized growth factors. That provided support and other requirements for the PGCs to develop.

"Hitting just the right elements to culture these cells was no simple matter. We built on earlier mouse studies, trying to do just enough to let the cells develop without going too far and becoming specialized," says Michael Shamblott, Ph.D., a Hopkins researcher.

PGCs, given the proper conditions, will develop into a tightly knit cluster of true pluripotent stem cells. The early indications were that the cells produced in the experiment were indeed stem cells. The cells displayed cell surface markers characteristic of stem cells, contained complete sets of normal chromosomes and produced enzymes typical of stem cells. The cells are also capable of many cell divisions.

"But the gold standard was seeing if the cells have true potential if they'd develop into the three basic layers of cells found in all mammalian embryos. And ours did," says Shamblott.

"The potential of these unique, versatile cells for human biologic studies and medicine is enormous," says John Gearhart, Ph.D., a professor of obstetrics/gynecology and of physiology at Johns Hopkins. "These cells will rapidly let us study human processes in a way we couldn't before. Instead of having to rely on mice or other substitutes for human tissues, we'll have a unique resource that we can start applying to medicine."

"Not only should scientists be able to generate specific nerve, muscle, skin or other cells for transplantation, but we should also be able to alter these cells, as has been done in mouse studies, to reduce the likelihood of rejection. We could make universal donors. More specific cells could become transplant therapies for diabetes, spinal cord injury, neurodegenerative disorders like Parkinson's disease, muscular dystrophies, atherosclerosis and wound healing," says Gearhart.

Ethical Considerations

The stem-cell research highlights many ongoing ethical debates. The use of human embryros as the source of the stem-cells is very controversial. Indeed, the US government had banned federal funding for this kind of research. Moreover, while many of the therapies envisioned for stem-cells involve cellular processes, these cells might also be used to facilitate germ-line gene therapies, an issue that has not been resolved.  

The University of Wisconsin study appears in the November 5, 1998 issue of Science. The Johns Hopkins study appears in the November 1998 issue of the Proceedings of the National Academy of Sciences. 

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