When some tissues are injured, cells may become de-differentiated, a reversal of differentiation. The de-differentiated cells form a mass of cells called a blastema, which, as healing proceeds, becomes once again differentiated into the type of cells which originally formed it. In order for regeneration of a limb or organ to take place, some of the specialized
cells making up the stump must de-differentiate, to return to an earlier stage of the DNA developmental program.
The electrochemical events controlling this process and that of healing are now becoming understood. Bone, for example, shows a piezoelectric property; that is, when bone is bent, an electric potential is created, with a negative charge on the concave side and a positive charge on the convex side.
New bone is laid down on the concave, electrically negative side, while old bone is removed from the convex, electrically positive side. In 1972, Dr. Becker and his associates reported the first successful stimulation of organized limb regeneration in mammals. The forelegs of rats were amputated between shoulder and elbow and an electrical stimulation device was implanted at the stump. Most of the animals regrew at least
part of the limb, while a few animals regenerated all tissues more or less properly from the stump down to the elbow. Using a similar technique in human patients with pseudoarthrosis (a persistent nonhealing condition of fractures), Dr. Becker achieved an 80-percent success rate in stimulating fracture healing. Dr. Stephen Smith in 1974 reported success in using
small direct electric currents (with an implanted electrode in the stump) to stimulate entire limb regeneration in adult frogs, which do not normally regenerate.
Dr. Bassett and his co-workers have successfully used low-average-power high-peak-power pulsed electromagnetic fields to accelerate the healing of fractured bones. They used coils energized by a battery powered semiconductor pulse generator attached externally over the area of the bone break. Bassett also used low-voltage electrical pulses produced externally by magnetic induction to treat adults and children with pseudoarthrosis (non-healing of fractures), with a high (80 percent) success rate.
The Wall Street Journal of 26 March 1979 reported that Bristol-Myers Zimmer Division has applied for FDA approval to market a device that stimulates healing of broken bones with direct electrical currents. Small:electrodes are implanted in the broken bone, a procedure which can be performed under local anesthesia.
FIRM HOPES TO MARKET BONE-GROWTH DEVICE
By a WALL STREET JOURNAL Staff Reporter
NEW YORK—Bristol-Myers Co. said it applied for federal approval to market a device that uses an electric current to stimulate regrowth of broken bones.
- The device is a product of research that in recent years shows
that broken bones tend to regrow and heal faster when they are
stimulated continuously by direct electrical current. The meth-
od appears particularly useful in so-called nonunion fractures in
which the bone is broken completely apart. Frequently, non-
union fractures require surgery to install a bone graft. —
Stimulation with direct current to induce the nonunion fracture to heal by regrowth avoids the need for bone-graft surgery. The procedure involves only implanting small electrodes to the broken bone, which can be done under local anesthesia.
Bristol-Myers said its Zimmer direct-current bone growth
stimulator was developed in conjunction with orthopedists at
the University of Pennsylvania medical school. The application
to market the device was made to the U.S. Food and Drug Administration by the company’s Zimmer USA subsidiary, a maker of surgical and hospital equipment.
Dr. Becker has studied potential (electrical voltage) differences between regenerating salamander limbs and those
of nonregenerating frogs. After amputation, the distal (distant
from the body) end of the limbs of both salamanders and frogs
become highly positive, but the salamander stump tip soon
becomes negative. Regeneration in the salamander proceeds
most rapidly during the period of greatest negativity, which
peaks at about two weeks. Becker found that the presence of
nerves is required for this electronegativity, which causes dedifferentiation. Interestingly, tumors are also de-differentiated, losing their specialized tissue properties. They behave
rather like de-differentiated cells in a wound which never re-
differentiate. Vitamin A can cause some epithelial cells (skin,
lung, and intestinal lining are examples) which have become
precancerous (de-differentiated) to revert to their differentiated normal state. Some tumors-have been regressed by the
use of electrical fields which stimulate regeneration.
“Reprinted by permission of The Wall Street Journal, copyright © Dow Jones and Com-
pany, Inc., 1979.
Recently, Dr. Clarence Cone has found that cells can bestimulated to divide by persistent electrical depolarization of the cell membrane (by causing sodium ions to flow into the cell). Even normally nondividing cells, such as neurons, divide when their membranes are depolarized for long enough. Experiments to learn more about how to control cell division, regeneration, differentiation, and tumor growth by this means are under way.
Part of the aging process suggested by Hayflick’s work on cell division, discussed in Part II, Chapter 10, is that irreversible differentiation may eventually block cell division and repair, thereby leading to senescence. It will be very interesting to find out whether the regeneration techniques of Bassett, Becker, Cone, and others can affect the limited number of
cell divisions found by Hayflick.
Dr. Bassett is currently experimenting with the use of electrical stimulation to regress cancer and to retard aging. At Columbia Presbyterian Hospital in New York City, he has an effective electrical stimulation clinic for patients with hard-to-heal broken bones. Perhaps the broken-hip problem which
permanently ends the active life of so many elderly people will succumb to electrotherapy combined with dihydroxy vitamin D. Electrobiology, Inc., a firm partly owned by Dr. Bassett, is currently selling electrical stimulation devices approved by FDA for use in fractures resistant to healing by
other therapies. These devices are said to be spreading widely
in use in the United States.
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