Healing wounds with cell therapy

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 white blood cells — the macrophages — and make them capable of accelerating cutaneous healing,” explained nephrologist Jean-Fran├žois Cailhier, a … Continue reading “Healing wounds with cell therapy”

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 white blood cells — the macrophages — and make them capable of accelerating cutaneous healing,” explained nephrologist Jean-Fran├žois 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 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 (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 diabetic patients 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 healing 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.

Open-access genetic screening for hereditary breast cancer is feasible, effective

Ms Sari Lieberman, a genetic counsellor at the Shaare Zedek Medical Centre, Jerusalem, Israel, will tell the annual conference of the European Society of Human Genetics that offering open-access BRCA testing to Ashkenazi women unaffected by cancer, regardless of their family history, enables the identification of carriers who would otherwise have been missed. Carrying one of the mutations for the BRCA genes means that women affected have a 50-80% risk of developing breast cancer and a 20-50% risk for ovarian cancer.

“We knew that half of these carriers have no family history of cancer, and therefore would not have been identified had the test been offered on the current personal and family history criteria,” she says. “As a genetic counsellor, it is frustrating and saddening to see the results of this policy, where patients are often only identified as BRCA carriers once they have been diagnosed with cancer.”

The researchers streamlined the pre-test process so that traditional genetic counselling, which can be time-consuming and difficult, was excluded. Instead they provided written information about the BRCA genes, the genetic test, and about the implications of being a carrier.

“Current strategies for testing focus on women who are 50 and older, which is not the optimal age for effective prevention. In order to address this, we would like to continue this study and look for other approaches that could include younger women,” says Ms Lieberman. participants in the study either referred themselves or were recruited by health professionals. Two-year follow up of the 1771 women tested included looking at psychosocial outcomes and health behaviours. Both groups reported a high level of satisfaction (94%) and low stress. Those who had referred themselves tended to be more knowledgeable about breast cancer issues than those who were recruited.

“Among the 25 women carriers we identified, 94% expressed satisfaction and 92% endorsed the idea of population screening. Their stress was understandably higher, but it declined over time, and their knowledge was greater than in non-carriers. All of them had breast surveillance, and three underwent risk-reducing bilateral mastectomy. Of those aged over 40, fifteen out of a total of 16 had their ovaries and Fallopian tubes removed in order to reduce risk,” Ms Lieberman reports.

The researchers say that their study provides convincing evidence that open access genetic testing overcomes major barriers; not just lack of family history, but also referral and bureaucratic barriers, and that it is acceptable to those likely to be affected and their families.

“We were concerned that ‘low risk’ participants, with no family history, might not be able to cope with being offered BRCA testing and particularly with positive test results. We also worried that being found not to be a carrier might provide false reassurance and cause women to think they had no cancer risk and therefore avoid standard surveillance. We were pleasantly surprised on both counts,” Ms Lieberman will say. In fact, mammography screening rates did not decline post-test in non-carriers, and even increased in some.

Falling prices for genetic sequencing and new techniques to avoid evaluating irrelevant gene variants will most likely make mutation screening available to wider populations in the near future. “We believe that our results are useful and highly relevant for other populations. On a personal note, I hope that this new approach means that one day I will not have to counsel someone with no family history and therefore no awareness of increased risk who says to me that she only wished she had known before,” Ms Lieberman will conclude.

Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University, Newcastle, United Kingdom, said: “This important study highlights the importance of population-wide genetic screening to identify women at risk of developing breast and ovarian cancer because of a genetic predisposition. The study also showed that most people cope very well with this genetic information; carriers of these mutations undertake breast cancer surveillance, whereas non-carriers are aware they can still develop breast cancer.”

Sedentary lifestyle appears to increase risk for both kidney and bladder cancer

The new research, published online ahead of print in the journal Cancer Epidemiology, details the findings of a hospital-based case-control study involving 160 patients with renal (kidney) cancer, 208 with bladder cancer and a control group of 766 people of the same ages who did not have cancer. A team led by Kirsten Moysich, PhD, MS, and Rikki Cannioto, PhD, EdD, MS, surveyed the participants in order to determine whether lifetime recreational physical inactivity was associated with risk of developing renal or bladder cancer.

Using multivariable logistic regression analysis, the team observed significant positive associations between lifetime recreational physical inactivity and cancer — 77% increased risk of developing renal cancer and 73% increased risk of developing bladder cancer. They found similar risk exposure among both obese and non-obese study participants, suggesting that the connection between inactivity and these cancers is not driven by obesity.

The data add to the growing body of evidence that physical inactivity may be an important and independent risk factor for cancer, the authors write, noting that larger studies are needed to substantiate the current findings and support conclusive determinations about these connections.

“We hope that findings like ours will motivate inactive people to engage in some form of physical activity,” says Dr. Moysich, senior author on the study and Distinguished Professor of Oncology in the Departments of Cancer Prevention and Control and Immunology at Roswell Park. “You don’t have to run marathons to reduce your cancer risk, but you have to do something — even small adjustments like taking the stairs instead of the elevator, walking around the block a couple of times on your lunch hour or parking the car far away from the store when you go to the supermarket.”

“Our findings underscore how important it is to maintain a healthy lifestyle, including getting and staying active,” adds Dr. Cannioto, Assistant Professor of Oncology in the Department of Cancer Prevention and Control at Roswell Park and first author on the new study. “The Department of Health and Human Services recommends 150 minutes each week of moderate physical activity or 75 minutes each week of vigorous physical activity as a way to generate significant, lasting health benefits.”