Scientists have developed a new therapeutic approach that could save diabetic patients from amputation by promoting wound healing.
Diabetic patients frequently have lesions on their feet that are very difficult to heal due to poor blood circulation. In cases of serious non-healing infections, a decision to amputate could be made.
“With this treatment, we can succeed in closing wounds and promoting healing of diabetic ulcers, we might be able to avoid amputations,” said Jean-Francois Cailhier, nephrologist at University of Montreal Hospital Research Centre (CRCHUM) in Canada.
We discovered a way to modify specific white blood cells – the macrophages – and make them capable of accelerating cutaneous healing, researchers said.
It has long been known that macrophages play a key role in the normal wound healing process. These white cells specialise in major cellular clean-up processes and are essential for tissue repair, researchers said.
They accelerate healing while maintaining a balance between inflammatory and anti-inflammatory reactions (pro-reparation).
“When a wound does not heal, it might be secondary to enhanced inflammation and not enough anti-inflammatory activity,” Cailhier said.
“We discovered that macrophage behaviour can be controlled so as to tip the balance towards cell repair by means of a special protein called Milk Fat Globule Epidermal Growth Factor-8, or MFG-E8,” Cailhier said.
Researchers 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.
The team then developed a treatment by adoptive cell transfer in order to amplify the healing process.
Adoptive cell transfer consists in treating the patient using his or her own cells, which are harvested, treated, then re-injected in order to exert their action on an organ.
This immunotherapeutic strategy is usually used to treat various types of cancer, researchers said.
This is the first time it has been shown to also be useful in reprogramming cells to facilitate healing of the skin, they said.
“We used stem cells derived from murine bone marrow to obtain macrophages, which we treated ex vivo with the MFG-E8 protein before re-injecting them into the mice, and we quickly noticed an acceleration of healing,” said Patrick Laplante, research assistant at CRCHUM.
“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,” Cailhier said.
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, researchers said.
This advanced personalised treatment could also make all the difference in treating cases of challenging wounds.
The study was published in the Journal of Investigative Dermatology.