Embryonic stem cells
Stem-cell research is now bearing fruit
FOURTEEN years ago James Thomson of the University of Wisconsin isolated stem cells from human embryos. It was an exciting moment. The ability of such cells to morph into any other sort of cell suggested that worn-out or damaged tissues might be repaired, and diseases thus treated—a technique that has come to be known as regenerative medicine. Since then progress has been erratic and (because of the cells’ origins) controversial. But, as two new papers prove, progress there has indeed been.
This week’s Lancet published results from a clinical trial that used embryonic stem cells in people. It follows much disappointment. In November, for example, a company in California cancelled what had been the first trial of human embryonic stem cells, in those with spinal injuries. Steven Schwartz of the University of California, Los Angeles, however, claims some success in treating a different problem: blindness. His research, sponsored by Advanced Cell Technology, a company based in Massachusetts, involved two patients. One has age-related macular degeneration, the main cause of blindness in rich countries. The other suffers from Stargardt’s macular dystrophy, its main cause in children. Dr Schwartz and his team coaxed embryonic stem cells to become retinal pigment epithelium—tissue which supports the rod and cone cells that actually respond to light—then injected 50,000 of them into one eye of each patient, with the hope that they would bolster the natural supply of these cells.
The result was a qualified success. First and foremost, neither patient had an adverse reaction to the transplant—always a risk when foreign tissue is put into someone’s body. Second, though neither had vision restored to any huge degree, each was able, four months after the transplant, to distinguish more letters of the alphabet than they could beforehand.
Whether Dr Schwartz’s technique will prove truly useful remains to be seen. Experimental treatments fail far more often than they succeed. But the second paper, published in Nature by Lawrence Goldstein of the University of California, San Diego, and his colleagues, shows how stem cells can be of use even if they do not lead directly to treatment.
Since 2006 researchers have been able to reprogram adult cells into an embryonic state, using proteins called transcription factors. Though these reprogrammed cells, known as induced pluripotent stem (iPS) cells, might one day be used for treatment, their immediate value is that they are also an excellent way to understand illness. Using them, it is possible to make pure cultures of types of cells that have gone wrong in a body. Crucially, the cultured cells are genetically identical to the diseased ones in the patient.
Dr Goldstein is therefore using iPS cells to try to understand Alzheimer’s disease. The brains of those with advanced Alzheimer’s are characterised by deposits, known as plaques, of a protein-fragment called beta-amyloid, and by tangles of a second protein, called tau. But how these plaques and tangles are related remains unclear. To learn more, Dr Goldstein took tissue from six people: two with familial Alzheimer’s, a rare form caused by a known genetic mutation; two with sporadic Alzheimer’s, whose direct cause is unknown; and two unaffected individuals who acted as controls. He reprogrammed the cells collected into iPS cells, then nudged them to become nerve cells.
In three of the four Alzheimer’s patients these lab-made nerve cells did, indeed, show higher levels of beta-amyloid and tau—and also of another characteristic of the disease, an enzyme called active GSK3-beta. Since he now had the cells in culture, Dr Goldstein could investigate the relationship between the three.
To do so he treated the cultured cells with drugs. He found that a drug which attacked beta-amyloid directly did not lead to lower levels of tau or active GSK3-beta; but a drug which attacked one of beta-amyloid’s precursor molecules did have that effect. That is useful information, for it suggests where a pharmacological assault on the disease might best be directed.
In the short term, at least, iPS-based studies of this sort are likely to yield more scientific value than clinical experiments of the type conducted by Dr Schwartz, even though they are not treatments in themselves. That will, though, require many more pluripotent cells. And at least one firm is selling a way to make billions of iPS cells for just that purpose. Its founder, appropriately, is Dr Thomson.