Healing wounds with cell therapy

May 29, 2017

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. A new therapeutic approach, presented recently in the Journal of Investigative Dermatology by Canadian researchers affiliated with the University of Montreal Hospital Research Centre (CRCHUM), could prevent these complications by promoting wound healing.

The solution isn't what you might expect, not just another antibiotic ointment or other prescription medication. It's the approach that's different, a way to heal through personalized medicine. "We discovered a way to modify specific - the macrophages - and make them capable of accelerating cutaneous healing," explained nephrologist Jean-François Cailhier, a CRCHUM researcher and professor at the University of Montreal.

It has long been known that macrophages play a key role in the normal wound healing process. These white 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).

"When a wound doesn't heal, it might be secondary to enhanced inflammation and not enough anti-inflammatory activity," explained Cailhier. "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."

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 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," said Dr. Patrick Laplante, Cailhier's research assistant and first author of the study.

Added Dr. Cailhier, "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. Indeed, as Dr. 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."

What now remains to be done is to test this personalized treatment using human cells. Thereafter, the goal will be to develop a program of human cell therapy for and for victims of severe burns. It will take several years of research before this stage can be reached.

This advanced personalized treatment could also make all the difference in treating cases of challenging wounds. According to the World Health Organization, diabetes affects 8.5% of the global population, and amputation rates of the lower extremities are 10 to 20 times higher in diabetics. "If, with this treatment, we can succeed in closing wounds and promoting healing of diabetic ulcers, we might be able to avoid amputations," Dr. Cailhier said.

"Serious burn victims could also benefit," he added. "By accelerating and streamlining the of burns, we may be able to reduce the infections and keloids that unfortunately develop much too often in such patients." Cancer patients requiring extensive reconstruction surgery could also benefit, he said.

Explore further: Macrophages need two signals to begin healing process

More information: Patrick Laplante et al, MFG-E8 Reprogramming of Macrophages Promotes Wound Healing by Increased bFGF Production and Fibroblast Functions, Journal of Investigative Dermatology (2017). DOI: 10.1016/j.jid.2017.04.030

Related Stories

Macrophages need two signals to begin healing process

May 12, 2017
In the immune system, macrophages act not only as soldiers responding to invading pathogens but also help rebuild the injured tissue once the infection is defeated. A new study by Yale Medical School researchers published ...

Researchers identify 'signal' crucial to stem cell function in hair follicles

May 24, 2017
Stem cell researchers at the University of Calgary have found another piece of the puzzle behind what may contribute to hair loss and prevent wounds from healing normally.

Breakthrough research discovery to help heal chronic wounds

December 14, 2012
(Medical Xpress)—The University of Queensland researchers have successfully restored wound healing in a model of diabetes paving the way for new treatments for chronic wounds.

New findings offer hope for diabetic wound healing

November 23, 2015
University of Notre Dame researchers have discovered a compound that accelerates diabetic wound healing, which may open the door to new treatment strategies. Non-healing chronic wounds are a major complication of diabetes, ...

Gene and stem cell therapy combination could aid wound healing

October 9, 2013
Johns Hopkins researchers, working with elderly mice, have determined that combining gene therapy with an extra boost of the same stem cells the body already uses to repair itself leads to faster healing of burns and greater ...

Study discovers new therapeutic target for diabetic wound healing

September 4, 2014
Research led by scientists in Dr. Song Hong's group at LSU Health New Orleans has identified a novel family of chemical mediators that rescue the reparative functions of macrophages (a main type of mature white blood cells) ...

Recommended for you

Image ordering often based on factors other than patient need: study

September 25, 2017
Do you really need that MRI?

Bone marrow concentrate improves joint transplants

September 25, 2017
Biologic joint restoration using donor tissue instead of traditional metal and plastic may be an option for active patients with joint defects. Although recovery from a biologic joint repair is typically longer than traditional ...

How ketogenic diets curb inflammation

September 25, 2017
Ketogenic diets – extreme low-carbohydrate, high-fat regimens that have long been known to benefit epilepsy and other neurological illnesses – may work by lowering inflammation in the brain, according to new research ...

Researchers develop treatment to reduce rate of cleft palate relapse complication

September 22, 2017
Young people with cleft palate may one day face fewer painful surgeries and spend less time undergoing uncomfortable orthodontic treatments thanks to a new therapy developed by researchers from the UCLA School of Dentistry. ...

Exosomes are the missing link to insulin resistance in diabetes

September 21, 2017
Chronic tissue inflammation resulting from obesity is an underlying cause of insulin resistance and type 2 diabetes. But the mechanism by which this occurs has remained cloaked, until now.

Thousands of new microbial communities identified in human body

September 20, 2017
A new study of the human microbiome—the trillions of microbial organisms that live on and within our bodies—has analyzed thousands of new measurements of microbial communities from the gut, skin, mouth, and vaginal microbiome, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.