continued from part one:

Embryonic Stem Cell Powers

Cell-signaling factors play a vital role in the development of the body
from a single egg and in guiding the emergence of the body's many different
cell types, including the vital stem cells that repair adult tissues. But
it is the stem cells that are the living clay from which the body is
sculptured and repaired.

Like clay, stem cells are dull and featureless. But they can morph into
blood, skin, bone or any of the body's other replaceable tissues. And they
retain the gift of self-renewal which, to curb the risk of cancer, is
withdrawn from all the body's mature cells.

Stem cells, when they divide, usually produce one mature cell and one stem
cell, thus maintaining their population numbers; mature cells produce
daughter cells identical to themselves and can divide only a limited number
of times, if at all. Stem cells last a long time, though they are not
immortal; mature cells cannot renew themselves.

Physicians are already drawing on the power of stem cells in a limited way,
as in bone marrow transplants for leukemia, which rely on the blood stem
cells in the marrow to regenerate the body's red and white blood cells, and
in skin grafts grown from a patient's cells. But these applications are
just a foretaste of those that some researchers expect.

In mice, where almost all stem cell technology is developed first,
biologists reported this year that they had reversed insulin-dependent
diabetes by implanting stem cells from the pancreas.
Researchers have even learned how to replace the tissues that normally are
not renewed, like heart muscle and the dopamine-producing cells of the
brain that are lost in Parkinson's disease. But this alchemy requires a
special class of stem cell known as embryonic stem cells.

Embryonic stem cells are created in the very early embryo; from them, all
the bodies' tissues and organs are generated. Once the body is formed, the
embryonic stem cells disappear, leaving behind a few descendants to keep
the body in good repair throughout its lifetime.

These descendants, often called adult stem cells, apparently lack the
embryonic stem cell's power of generating any and all of the body's
tissues. Nor can they renew themselves indefinitely, as can embryonic stem
cells grown in glassware.

Biologists are exploring two separate ways of harnessing the regenerative
powers of stem cells, one through embryonic stem cells and the other by
using of adult stem cells. Each route has different advantages.

Human embryonic stem cells carry an ethical burden in that they are derived
by destroying an embryo, although one due to be discarded by the fertility
clinic where it was created. The embryo at this stage has no fetuslike
features; it is a microscopic sphere of cells that holds an inner clump of
cells destined to form all the tissues of the embryo.

These cells, grown in the laboratory for the first time in 1998, were
approved for use by government-supported researchers in August after
sustained opposition from opponents of abortion.

The promise of embryonic stem cells is that in principle they can be coaxed
to develop into any desired tissue.

Researchers at Indiana University showed in 1996 that mouse embryonic stem
cells could be nudged down the lineage that leads to heart muscle cells and
implanted in mice, where they would graft themselves seamlessly into the
animal's heart.

Biologists at Geron, of Menlo Park, Calif. have succeeded in making human
embryonic cells develop into heart muscle cells.

The field of human embryonic stem cells is for the moment dominated by
Geron, which, under its visionary founder Dr. Michael West, financed the
research that led to the isolation of the cells.

The company also controls two other pieces of biological wizardry. It has
formed an alliance with PPL Therapeutics of Edinburgh, which has rights to
the nuclear transfer techniques used to create the cloned sheep Dolly. And
it owns the rights to a human protein called telomerase.

Probably as an anticancer mechanism, cells possess a division- counter that
forces them into senescence after they have divided about 50 times.
Telomerase can confer the gift of immortality on cells because it sets
their division counter back to zero. In the body, it is found in cells with
a limitless ability to divide — egg and sperm cells, and cancer cells.

In the pursuit of generating fully youthful replacement tissues to repair
old bodies, Geron has three powerful techniques to bring to bear.

One is to extract adult stem cells from the patient, immortalize them with
telomerase and return a fully youthful cell infusion or tissue to the patient.

Second, replacement tissues could be generated from human embryonic cells
by driving them down the appropriate lineages with cytokines and other agents.

Third, if such tissues prove too provocative to patients' immune systems,
Geron is working on ways to generate embryonic cells from patients' own
mature cells. The company hopes to identify factors that reprogram human
cells back to the embryonic state. A patient could then be treated with
tissues made from his or her own embryonic cells.

Adult Stem Cells

Meanwhile other biologists have been pursuing the study of adult stem
cells. The cells have long defied discovery because they are very hard to
distinguish from other cells and because they hide out in special sites,
which are only now being identified.

The source of the brain's stem cells was discovered only last year — in the
lining of the brain's fluid-filled ventricles — and the skin stem cells'
hideout was identified this August as a special pocket half-way up the root
of the hair follicles that stud the skin.

About 20 different types of adult stem cell have now been identified with
varying degrees of confidence. In the body, each type seems dedicated to
replenishing its own tissue: neural stem cells make new brain cells, bone
marrow cells make only red and white blood cells.

In laboratory experiments, however, several types of adult stem cells seem
able to take on other types' roles; perhaps, with the right signals, an
adult stem cell will repair any tissue, not just its own.

The degree of versatility of adult stem cells may prove an important
clinical issue because bone marrow stem cells, for example, are easier to
harvest from a patient than neural stem cells, and might in that case prove
a preferable source of cells to treat, say, Parkinson's disease.

Treating patients with cells derived from their own stem cells would avoid
any problems of immune rejection. But adult stem cells can divide only a
finite number of times and in older or diseased patients may have a limited
lifetime left.

Embryonic cells, however, have their division timers set back to zero.
Tissues derived from them would be perhaps healthier and certainly more
youthful than the patient's own. Their possible drawback is that of being
rejected by the patient's immune system.

But embryonic stem cells and adult stem cells seem much less provocative to
the immune system than mature cells, so the risk of rejection may be minimal.

One of the most intriguing aspects of stem cells is their ability to
integrate themselves into target tissues and turn into cells of the right
type. This property, known as engraftment, holds out the possibility that
stem cells can be put to therapeutic use long before their behavior is
fully understood.

On the harbor waterfront in Baltimore, in a building that was once a tuna
cannery, a company called Osiris Therapeutics — after the ancient Egyptian
god of regeneration and immortality — is working to unlock the restorative
powers of a special kind of adult stem cell.

Called bone marrow stromal cells by some biologists and mesenchymal stem
cells by Osiris, these obscure cells serve as the glue that keeps the body
together because they repair the connective tissues of bone, tendon,
cartilage and muscle. The cells also make the stroma, or support, on which
the blood- forming cells of the bone marrow grow.

Osiris's probable first product, now in clinical trials, is an infusion of
mesenchymal stem cells for patients undergoing bone marrow transplants. The
mesenchymal stem cells find their way to the bone marrow and build stroma,
enabling patients to return home several days earlier than otherwise.

Mesenchymal cells grown in glassware can be induced to develop into
different types of mature cell. Cultured on bone material, they will form
bone cells; in a gel, they grow into cartilage-making cells.

Osiris has a bone-making preparation of stem cells, Osteocel, in clinical
trials, and is working with animals to develop cartilage-making cells for
joint repair and heart muscle cells for heart attack victims.

If mesenchymal stem cells prove as effective as hoped in repairing bone,
tendon and cartilage, says the company's chief executive, Dr. Annemarie
Moseley, "Patients in middle age would come in, before the degenerative
process starts, and would get a cell or tissue implant, and degeneration of
the structural elements would no longer be part of the aging process."

Making Lives Longer

Companies pursuing regenerative medicine in its various forms are reluctant
to talk about extending the maximum human life span, a project that has
acquired ill-repute in the past. "Our objective is to increase health span,
not life span," said Dr. Okarma, Geron's chief executive. "Our hope would
be that our children live a great fraction of their life in wellness,"

But Dr. Michael West, Geron's founder and now chief executive of Advanced
Cell Technology, has always had the goal of longer life in mind. "When I
hear critics saying they don't want to see life span extended, they are
thinking about the old myth of Tithonus where people live longer in a
decrepit state. That's not what we are talking about doing. As long as
people are wanted and happy, I think it's a very noble goal and we should
strive for that, and regenerative medicine is one of the means to achieve it."

In the myth to which Dr. West refers, a Greek youth beloved by the goddess
of the dawn made the error of asking her for gift of eternal life instead
of eternal youth. Later, bowed by miseries of age to which death could not
put a natural end, Tithonus begged her to withdraw her gift, something that
even Greek gods could not do. She did, however, provide the apparent
consolation of turning him into a grasshopper.

Having learned the grasshopper lesson, the pioneers of regenerative
medicine aspire to renew individual tissues, at least as their primary
goal. Their concept is far from proved, but it rests on a set of
interesting scientific advances, has attracted considerable investment and,
just possibly, may one day revolutionize many areas of medicine.


By NICHOLAS WADE
Copyright 2000 The New York Times Company
http://www.nytimes.com/2000/11/07/science/07MEDI.html

janet paterson, an akinetic rigid subtype parkie
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