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.
