New Technology for Accelerated Wound Healing Discovered

Researchers at Uppsala University and SLU have found a new way of accelerating wound healing. The method published in the highly ranked journal PNAS involves using lactic acid bacteria as vectors to produce and deliver a human chemokine in the wounds. The research group is the first in the world to have developed the concept for topical use and the technology could turn out to be disruptive to the field of biologic drugs.

sperm, brain tumours, Common drugs, diabetes, chronic wounds, magnetism, intestinal tumours, molecular scissors, disease, genetic, immune cells, drug development, Diabetes, Antibiotic, hydrogen generation, chronic obstructive pulmonary disease, malaria, photosynthesis, kidney failure, Brain tumours, mental health, blood cancer, cancer, dementia, cancer treatment, antibiotic resistance, blood vessel leakage, quantum simulations, atrial fibrillation, batteries, goiter treatment, terahertz radiation, organic materials , Guild of European Research Intensive Universities, gene copies, social anxiety, blue light screens, ‘Our hope is that these findings will make it possible to discover a way to selectively inhibit the TGF-beta signals that stimulate tumour development without knocking out the signals that inhibit tumour development, and that this can eventually be used in the fight against cancer,’ says Eleftheria Vasilaki, postdoctoral researcher at Ludwig Institute for Cancer Research at Uppsala University and lead author of the study. TGF-beta regulates cell growth and specialisation, in particular during foetal development. In the context of tumour development, TGF-beta has a complicated role. Initially, it inhibits tumour formation because it inhibits cell division and stimulates cell death. At a late stage of tumour development, however, TGF-beta stimulates proliferation and metastasis of tumour cells and thereby accelerates tumour formation. TGF-beta’s signalling mechanisms and role in tumour development have been studied at the Ludwig Institute for Cancer Research at Uppsala University for the past 30 years. Recent discoveries at the Institute, now published in the current study in Science Signaling, explain part of the mechanism by which TGF-beta switches from suppressing to enhancing tumour development. Uppsala researchers, in collaboration with a Japanese research team, discovered that TGF-beta along with the oncoprotein Ras, which is often activated in tumours, affects members of the p53 family. The p53 protein plays a key role in regulating tumour development and is often altered – mutated – in tumours. TGF-beta and Ras suppress the effect of mutated p53, thereby enhancing the effect of another member of the p53 family, namely delta-Np63, which in turn stimulates tumour development and metastasis.

Treatment of large and chronic wounds are a high cost burden to the health care system since effective tools to accelerate healing are lacking. Wound care is today limited to mechanical debridement, use of different dressings and significant amounts of antibiotics preventing or treating wound infections. With the aging population, occurrence of chronic diseases such as diabetes and the alarming global spread of antibiotic resistance, a treatment that kick-starts and accelerates wound healing will have a significant impact. There have been many attempts to solve the problem of chronic wounds that have failed. Drug candidates currently in late stage clinical trials comprise of growth factors, which are traditional protein-based biological drugs associated with high costs, and some trials have been prematurely terminated.

“We have developed a drug candidate, a next-generation biologic medical product, and are now publishing the fantastic results from the preclinical part where wound healing was strongly accelerated in mice,” says Mia Phillipson, Professor at the Department of Medical Cell Biology, Division of Integrative Physiology, Uppsala University.

The acceleration of the healing process occurs due to changes in the microenvironment in the wound, which change the behaviour of specific immune cells. With the newly developed technology, the researchers can increase the level of a chemokine, CXCL12, for a sufficient time period through continuous delivery directly to the wound surface. In addition, bioavailability of CXCL12 is synergistically increased within the wound as the bacterial produced lactic acid causes a slight pH drop that inhibits degradation.

“The chemokine, CXCL12, is endogenously upregulated in injured tissue and by increasing the levels further, more immune cells are recruited and are more specialised to heal the wound, which accelerates the whole process,” says Professor Phillipson.

The potent effect on acceleration of wound healing is demonstrated in healthy mice but also in two models of diabetes, one model of peripheral ischemia as well as in a model using human skin biopsies.

There were clear differences in the composition of immune cells in the wounds and the immune cells present produced higher levels of TGFß at earlier time points. The treatment was local without systemic exposure.

“This is very exciting from a health care perspective. We have a technology that works and now understand the mechanism behind it, how it accelerates wound healing. The next step is a study in a pig model,” says Professor Phillipson.

Source : Uppsala University