AsianScientist (July 27, 2017) – Scientists in India have found that a common anti-inflammatory drug, celecoxib, promoted the survival of stem cells injected into chronic wounds to aid in wound repair. Their study is published in Cytotherapy.
Chronic wounds are those that do not heal easily. In patients with diabetes, chronic wounds can lead to serious complications and, in some cases, may eventually mean that doctors have to amputate the affected limb.
“Curing chronic wounds in patients with diabetes, or in those undergoing chemotherapy and radiotherapy, is a constant challenge,” said Dr. Amitava Das of the Academy of Scientific & Innovative Research, located at the Council of Scientific & Industrial Research-Indian Institute of Chemical Technology in Hyderabad, India.
Conventional treatments for inflamed, chronic wounds often fail, so scientists are devising new treatments. Stem cells—cells that can change into other cell types, including skin cells—may be injected into the wound to help with the healing process. However, there are hurdles to making stem cell treatments work.
“Stem cell therapy holds a lot of promise but its use is limited by the harsh inflammation in the wound environment,” said Das.
Inflammation is normal in wound healing. At the wound site, enzymes such as cyclooxygenase-2 (COX-2) become more active and contribute to the inflammation. This inflammation is important to stimulate changes in tissue growth and blood flow which allow the tissue to heal. However, in chronic wounds, inflammation is more extensive and prolonged, and this can be lethal to stem cells injected into the wound. This is one of the reasons why, so far, stem cells have not worked as a treatment for chronic wounds.
Das and his colleagues hypothesized that celecoxib, a common anti-inflammatory drug that selectively inhibits COX-2, would improve stem cell survival and treatment outcomes for chronic wound therapy.
To test their hypothesis, the group used an experimental mouse model of chronic skin wounds. They found that in mice receiving an oral dose of celecoxib together with stem cell injections into their wounds, the stem cells showed better wound healing properties and promoted more tissue growth compared with untreated mice, or mice treated using stem cells or celecoxib alone.
A significantly higher amount of stem cells had survived and integrated into the wound tissue in mice that had received celecoxib. There were also fewer inflammatory white blood cells and lower levels of inflammatory molecules such as interleukin-17A in their wounds.
The researchers also showed that interleukin-17a was responsible for activating a type of immune cell, the macrophages, that attacked and killed stem cells in the wound. By inhibiting the COX-2 enzyme, and consequently inhibiting interleukin-17A, celecoxib prevented macrophages from killing the injected stem cells. Moreover, celecoxib directly increased stem cell differentiation into skin cells.
Stem cell treatments for chronic wounds could thus be more effective if patients simply took anti-inflammatory drugs during treatment.
“With these findings, we could overcome some of the limitations to successful stem cell therapy for chronic wounds,” said Das. “I personally feel that the present findings have provided a ray of hope for patients with chronic wounds. We have also been able to identify the molecular targets responsible for these effects, and this could help scientists to identify new drugs that could also help.”
The article can be found at: Geesala et al. (2017) Cox-2 Inhibition Potentiates Mouse Bone Marrow Stem Cell Engraftment and Differentiation-mediated Wound Repair.
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Source: Elsevier; Photo: Pixabay.
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