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View From the Lab: Harnessing Stem Cells
Insights From Harvard Medical School

By Anthony L. Komaroff, M.D., and George Q. Daley, M.D., PH.D.
Newsweek
Updated: 2:34 p.m. ET Nov. 28, 2004


Dec. 6 issue - How does a child with type 1 diabetes resemble a 60-year-old
heart-attack victim or an 80-year-old Parkinson's patient? Outwardly their
conditions have little in common, yet they share a critical feature. All
three involve the loss of a single type of specialized cell that the body
can't replace on its own. Cell depletion is the root cause of many major
diseases, from Alzheimer's to heart failure. And though treatment can often
ease the symptoms, it rarely solves the underlying problem. That's why
researchers are so keen on the potential of stem cells. Cultivated and
administered in the right ways, these all-purpose precursors could
conceivably replenish any tissue an ailing patient lacked. The challenge-and
it's not a small one-is to learn to direct their development.

Every cell in the body houses the same collection of about 25,000 genes, but
different genes are active in different types of cells. Gene activity is
what distinguishes a heart cell from a brain cell or a kidney cell. The stem
cells in a 5-day-old embryo can develop into any of these specialized cell
types, but this "pluripotent" state doesn't last long. As a stem cell picks
up chemical signals from its surroundings, different genes get switched on
or silenced, and the cell becomes more specialized. Specialized cells can no
longer switch roles as needed, and few can reproduce. That's why heart
attacks and brain injuries are so devastating. They leave the injured organ
powerless to repair itself.

Stem-cell therapy could change that, but researchers still face several
hurdles. The first is to learn more about how cells develop and specialize.
Suppose you wanted to turn a stem cell into a neuron that could manufacture
dopamine, the brain chemical that Parkinson's patients lack. Which of the
cell's 25,000 genes would you activate? Which ones would you silence? And
how would you orchestrate all this activity? The task may sound
overwhelming, but the science is evolving rapidly. Researchers have already
used stem cells to treat Parkinson's, diabetes and spinal-cord injuries in
mice, and few experts doubt that stem-cell therapy will one day be feasible
in people.

Unfortunately, feasible doesn't always mean practical. Right now, human
embryos are the only reliable source of high-quality pluripotent stem cells.
Researchers harvest them from embryos that fertility clinics would otherwise
discard, but that practice is controversial and the supply is finite, so
experts are eager to find new sources of stem cells. The partially
specialized stem cells found in bone marrow and some other adult tissues are
useful for certain tasks, such as replenishing blood cells destroyed by
chemotherapy. Unfortunately, they aren't nearly as versatile as embryonic
cells.


A technique known as nuclear transfer, or "therapeutic cloning," may someday
provide you with your own personal supply of embryonic stem cells. Doctors
would extract an egg from a woman's ovaries, then remove the nucleus and
replace it with the nucleus from one of your cells. The egg, which now
contains your genes, would divide and, after several days, develop into a
200-cell blastocyst. Cells from the blastocyst would be extracted and left
to multiply in a laboratory dish. These cloned cells could be used to repair
your tissues. And unlike stem cells plucked from fertility clinics, they
would never be rejected by your immune system.

None of these techniques will revolutionize medicine this year or next, but
the pace of discovery is accelerating. In South Korea, researchers have
started to conduct human experiments with nuclear transfer. The ethics
debates are sure to continue, and they should. Because stem-cell therapy is
no longer an idle fantasy-it's a revolution waiting to happen.

Komaroff is editor in chief of Harvard Health Publications; Daley conducts
stem-cell research at Harvard Medical School and the Children's Hospital
Medical Center. For more information, go to health.harvard.edu/NEWSWEEK.

C 2004 Newsweek, Inc.
URL: http://msnbc.msn.com/id/6596811/site/newsweek/



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