An experimental treatment in mice allows the
reprogramming of blood cells to promote the healing process of cutaneous
wounds. This new therapeutic approach could prove to be beneficial in
healing challenging wounds—such as those due to severe burns and
diabetes-related foot ulcers. The work,
by researchers affiliated with the University of Montreal Hospital
Research Centre (CRCHUM), Canada, was published online May 16 in the Journal of Investigative Dermatology.
“We
discovered a way to modify specific white blood cells—the
macrophages—and make them capable of accelerating cutaneous healing,”
said nephrologist Jean-François Cailhier, MD, PhD, a CRCHUM researcher
and professor at the University of Montreal.
Macrophages
specialize in major cellular clean-up processes and are essential for
tissue repair; they accelerate healing while maintaining a balance
between inflammatory and anti-inflammatory reactions (pro-reparation).
“We
discovered that macrophage behavior can be controlled so as to tip the
balance toward cell repair by means of a special protein called Milk Fat
Globule Epidermal Growth Factor-8, or MFG-E8,” said Cailhier.
Cailhier’s
team first showed that when there is a skin lesion, MFG-E8 calls for an
anti-inflammatory and pro-reparatory reaction in the macrophages.
Without this protein, the lesions heal much more slowly. Then the
researchers developed a treatment to amplify the healing process by
using adoptive cell transfer, which consists of treating the patient
using his or her own cells. The cells are harvested, treated, then
re-injected to exert their action on an organ. This immunotherapeutic
strategy is usually used to treat various types of cancer. This is the
first time its usefulness in reprogramming cells to facilitate healing
of the skin has been demonstrated, the team said.
The patient (in
this case the mouse) is not exposed to the protein itself. As Cailhier
explained, “if we were to inject the MFG-E8 protein directly into the
body there could be effects, distant from the wound, upon all the cells
that are sensitive to MFG-E8, which could lead to excess repair of the
skin causing aberrant scars named keloids. The major advantage [of this
treatment] is that we only administer reprogrammed cells, and we find
that they are capable of creating the environment needed to accelerate
scar formation. We have indeed discovered the unbelievable potential of
the macrophage to make healing possible by simple ex vivo treatment.”
Testing
using human cells remains to be done. Thereafter, the goal will be to
develop a program of human cell therapy for patients with diabetes and
for people who have experienced severe burns. It will take several years
of research before this stage can be reached.
“By accelerating
and streamlining the healing of burns, we may be able to reduce the
infections and keloids that unfortunately develop much too often in such
patients,” Cailhier said. “If, with this treatment, we can succeed in
closing wounds and promoting healing of diabetic ulcers, we might be
able to avoid amputations.”
Editor’s note: This story was adapted from materials provided by CRCHUM.
