Medical Device Daily Contributing Correspondent
And MDDs
LONDON – Human cells use at least two gene products to respond to electric fields created by ion flow, which help to heal wounds, researchers have found.
The molecules control a type of cell migration called electrotaxis and activate signalling pathways similar to those identified for chemotaxis.
Min Zhao, professor of biomedical sciences at the School of Medical Sciences and Department of Ophthalmology at the University of Aberdeen (Aber deen, Scotland), told Medical Device Daily's sister publication BioWorld International: “These discoveries offer a novel perspective in wound-healing research and management. Endogenous electric fields clearly have a significant role in guiding cell movement in wound healing.
“This effect is mediated by a couple of key molecules, which have been shown as 'compass molecules' in chemotaxis, the directional cell movement in response to chemical gradients.”
Now that the molecules mediating electrotaxis have been identified, he added, it may be possible to develop new approaches to wound management. Zhao and his colleagues – including collaborators in Austria, the U.S. and Japan – are working with clinical teams to develop new treatments.
The work is reported in the July 27, 2006, issue of Nature in a paper titled “Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN.”
Endogenous electric fields around wounds were first detected more than 150 years ago by the German physiologist Emil Du-Bois Reymond. More recent studies have shown that disruption of an epithelial layer instantly generates endogenous electric fields, proposed as important in wound healing. The electric fields are created by ion pumps, which move ions of positive or negative charge in particular directions.
Using an in vitro model of a wound in corneal epithelium, without applying an electrical field, Zhao and his team showed that cells moved into the wound in a coordinated manner. When they applied an electrical field with a polarity opposite to that normally observed in a natural wound, the cells migrated in the opposite direction, and the wound opened up instead of beginning to heal. Increasing the strength of the field (using the normal polarity) increased the speed of cell movement into the wound.
The experiments led to the conclusion that electrical signals guide and stimulate the migration of inflammatory cells, fibroblasts and epithelial cells in wound healing. And subsequent studies showed that electric fields could induce signaling cascades similar to those involved in chemotaxis. Certain signaling molecules became located at the leading edge of migratory cells, when the cells were exposed to an electric field.
A molecule called p110gamma appeared to be important in the process. When Zhao and his colleagues disrupted the copy of the gene encoding p110gamma in the cells, they found that the signalling molecules no longer responded to the electric field in the same way. In particular, when the cells were cultured in assays designed to assess cell migration, the cells no longer migrated in response to an electric field.
The team concluded: “These data show that [the protein made by the gene p110gamma] controls electrotaxis and provides the first identification of a gene, p110gamma, that controls electric-field-induced cell migration.” Further experiments showed that the product of a gene called phosphatase and tensin homologue (Pten) also is required for electrotaxis-regulated wound healing.
Zhao explained: “We found that the protein encoded by p110gamma, which is called PI3 kinase (gamma) catalytic subunit, when activated, sends a signal down within the cell, which results in actin polymerization. Actin polymerization in turn pushes the cell membrane, enabling the cell to move in that direction.”
The second gene, Pten, he said, is a negative regulator of PI3 kinase signaling.
NFC key to meter-pump concept device
Cambridge Consultants (Cambridge, UK) reported on a medical device concept for managing diabetes that uses Near Field Communication (NFC), the close-proximity wireless communications standard, to integrate glucometers and insulin pumps.
The prototype device, developed in conjunction with Royal Philips (Amsterdam, the Netherlands), demonstrates how NFC can be used to simplify treatment for diabetics, and could be the first of a new generation of medical devices using close-proximity wireless communications.
Jointly developed by Philips and Sony Electronics (Park Ridge, New Jersey), NFC is a combination of contactless identification and interconnection technologies that enables secure short-range communication between electronic devices, such as mobile phones, PDAs and computers via fast wireless connection.
NFC operates in the 13.56 MHz frequency range, typically over a few centimeters distance and combining the functions of a contactless reader, a contactless card and peer-to-peer functionality on a single chip.
The concept diabetes system wirelessly links a glucometer with an insulin pump. The glucometer records the blood sugar reading and then recommends a bolus dose of insulin. If the patient accepts the dose, then he or she simply swipes the glucometer against the insulin pump, and the drug is delivered.
This confirmation feature, which Cambridge Consultants dubs “patient-in-the-loop dosing,” enhances confidence and allows the user to modify dosage calculations for lifestyle reasons.
Cambridge Consultants said it believes that NFC adds characteristics that inspire user confidence in medical applications, including a more ergonomic process with a simple user interaction, improved accuracy of dosing, data logging for compliance monitoring, and the ability to make devices much more discreet.
Richard Traherne, head of wireless communication from Cambridge Consultants, said: “[W]e see strong potential for the technology in a wide array of medical applications including pain relief, asthma and respiratory care, gastric electrical stimulation therapy, and treatments for congestive heart failure or urinary urge incontinence.”