Posted on Jul 19, 2005, 10 a.m.
By Bill Freeman
The body's innate capacity for regeneration is what all stem cell therapies strive to emulate and improve upon. For that reason, the simplest route to many treatments may involve recruiting and activating the stem cells already hiding within our tissues. A major medical research effort now focuses on learning the subtle chemical language that directs stem cell behaviour during natural wound healing.
The body's innate capacity for regeneration is what all stem cell therapies strive to emulate and improve upon. For that reason, the simplest route to many treatments may involve recruiting and activating the stem cells already hiding within our tissues. A major medical research effort now focuses on learning the subtle chemical language that directs stem cell behaviour during natural wound healing. Mastering this idiom could in some cases help to eliminate the need for therapeutic infusions of lab-grown cells. The right chemical cues might even restore the vigour to cells in older patients. The potential benefits are many--but there are also dangers.
To see the benefits, consider the aftermath of an overzealous workout that leaves muscles screaming in pain. Individual muscle cells release chemical signals as their own cry for help. Homing to the sites of microscopic tears in the muscle fibres, the stem cells then immediately get to work making repairs.
Early this year a newly discovered protein dubbed Delta was credited with rejuvenating the muscle-building stem cells of mice. A group led by Stanford University's Thomas Rando paired old and young mice, connecting their circulatory systems so that the old mice had the youngsters' blood running through their veins. Rando found that something in the young blood, purportedly the Delta protein, restored youthful activity levels to stem cells belonging to the old mice.
Researchers have in the past successfully regenerated muscle mass in animals through experimental gene therapies that deliver a different protein, called insulinlike growth factor-1 (IGF-1). (Indeed, the experiments worked so well they have triggered fears that future athletes will engage in "gene doping".) IGF-1 both triggers stem cell activity and, when its call is amplified, can summon stem cells from afar to the site of an injury. Rather than requiring transplanted stem cells to regenerate tissue damaged by a heart attack, therefore, some researchers believe a dose of IGF-1 could kick-start repairs by stem cells already circulating in the bloodstream or hiding within the heart itself. A similar approach might work in any number of organs or tissues, provided scientists can learn which signals call the correct stem cells to duty.
But even more important may be knowing how to shut the stem cells off when the repairs are done. One of the darker revelations to have come from stem cell research in recent years is the connection to some varieties of cancer. At least one leukaemia is known to be caused by bone marrow stem cells gone awry. Certain brain, stomach and breast cancers are also now suspected to be triggered by stem cells turned malignant.
One theory holds that this may happen when stem cells, which are usually dormant, get stuck in wound-repair mode. Remaining activated too long makes the stem cells vulnerable to genetic mutations, and then they can become a biological nightmare: a rogue cancer cell with a stem cell's proliferation power.
Yet researchers are already finding ways to turn the stem/cancer cell connection back to patients' advantage. The homing instinct of stem cells has been exploited in animal experiments to deliver a "suicide gene" to tumour cells, leaving normal tissues unharmed. The physical similarities of cancer and stem cells also recently led to a mechanical test that makes it easier to find both types of cell in a person's blood. And, of course, widespread attempts to parse the signalling language of stem cells in order to turn a patient's own healing powers on may also reveal commands that turn tumour cells off.
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