Stanford researchers observe 25th anniversary of stem cell identification and purification

By Christopher Vaughan

The 1988 Science paper was also a landmark result in that Weissman and his colleagues developed novel assays to show the full regeneration of all blood cell types,  developed new techniques for purifying stem cells and provided the most accurate description yet of the particular cell-surface markers that defined HSCs.

“The 1988 Science article extended previous work by defining a broadly applicable approach to the identification and isolation of mouse HSC, and by establishing a new transplant model,” says Gerald Spangrude, who was first author on the 1988 paper and is now a professor at the University of Utah School of Medicine. The Weissman lab established a robust model system for analysis of HSC that still persists 25 years later, he says. “Virtually every modern study of mouse HSC biology in the literature today utilizes some or all of the innovations introduced by the landmark 1988 study.”

As part of the celebrations surrounding the California Institute for Regenerative Medicine’s World Stem Cell Awareness Day, researchers and staff at the Stanford Institute for Stem Cell Biology and Regenerative Medicine are observing the 25th anniversary of the first isolation of stem cells in a highly purified form. In 1988, institute director Irv Weissman published a paper documenting their identification and purification of the mouse blood stem cell. This was the first time that any stem cell (other than embryonic stem cells) from any species had been identified and isolated in such a concentrated form.  The publication of that paper in the July 1, 1988 issue of the journal Science in many ways marked the beginning of a new era in stem cell research and medicine, the researchers say.

Oct 2, 2013

After the 1988 Science paper, Weissman and his colleagues went on to identify and purify human HSCs as well as stem cells for many other kinds of tissues in humans as well as animals.
These discoveries set the stage for stem cell-based therapies of intractable diseases.  In a clinical trial of a therapy for women with stage IV breast cancer, Weissman and his colleagues first gave the women high-dose chemotherapy to rid them of cancer, then transplanted the women’s own purified, cancer-free blood stem cells back into them. Those women in this Stanford clinical trial showed a 33% survival rate about 15 years after treatment, a rate that is much higher than conventional therapies. Clinical trials with human brain-forming are currently ongoing for both spinal cord injury and a variety of pediatric congenital neurodegenerative diseases. And the demonstration by Weissman and others that leukemias have their own stem cell hierarchy has led to the isolation of leukemia stem cells and identification of cancer therapeutic targets that are now the subject of immunotherapy trials.

Stem cells, which can reproduce themselves as well as produce highly specialized tissues, are very rare. Among a sample of serum isolated from the bone marrow, only about 1 in 10,000 to 20,000 cells are true hematopoietic (blood) stem cells (HSCs). Before the Weissman lab’s work, other researchers had begun to increase the concentration of related cells, but they had not yet purified stem cells themselves. To prove that they had isolated stem cells, the researchers showed that their purified cells could not only reproduce, but could also generate all blood cell types.

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