Modifying Macrophages to Accelerate Healing

The immune cells called macrophages play an important role in the healing of injuries. Their activities appear to be the key to examples of exceptional regeneration in mammals, for example. This may have something to do with their clearance of the transient senescent cells generated during regeneration, or may be related to other signaling processes. Researchers have in previous years shown that adjusting the behavior of macrophages can alter the pace at which wounds heal, and it is hoped that this might be a compensatory approach capable of reducing the loss of regenerative capacity that occurs with aging. Here is a recent example of work that runs along the same lines:

It has long been known that macrophages play a key role in the normal wound healing process. These cells 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. "When a wound doesn't heal, it might be secondary to enhanced inflammation and not enough anti-inflammatory activity. We discovered that macrophage behaviour 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."

The 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. Then the researchers 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. This is the first time it has been shown to also be useful in reprogramming cells to facilitate healing of the skin.

"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. The MFG-E8 protein, by acting directly upon macrophages, can generate cells that will orchestrate accelerated cutaneous healing. The beauty of this therapy is that the patient (in this case the mouse) is not exposed to the protein itself. 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."



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