Elsevier

European Journal of Pharmacology

Volume 843, 15 January 2019, Pages 307-315
European Journal of Pharmacology

Review
Novel trends in application of stem cells in skin wound healing

https://doi.org/10.1016/j.ejphar.2018.12.012Get rights and content

Abstract

The latest findings indicate the huge therapeutic potential of stem cells in regenerative medicine, including the healing of chronic wounds. Main stem cell types involved in wound healing process are: epidermal and dermal stem cells, mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs) and hematopoietic stem cells (HSCs).

In the therapy of chronic wounds, they can be administrated either topically or using different matrix like hydrogels, scaffolds, dermal substitutes and extracellular matrix (ECM) derivatives. Stem cells are proven to positively influence wound healing by different direct and indirect mechanisms including residing cells stimulation, biomolecules release, inflammation control and ECM remodelling. MSCs are especially worth mentioning as they can be easily derived from bone-marrow or adipose tissue.

Apart from traditional approach of administering living stem cells to wounds, new trends have emerged in recent years. Good healing results are obtained using stem cell secretome alone, for example exosomes or conditioned media. There are also attempts to improve healing potential of stem cells by their co-culture with other cell types as well as by their genetic modifications or pretreatment using different chemicals or cell media. Moreover, stem cells have been tested for novel therapeutic purposes like for example acute burns and have been used in experiments on large animal models including pigs and sheep.

In this review we discuss the role of stem cells in skin wound healing acceleration. In addition, we analyse possible new strategies of stem cells application in treatment of chronic wounds.

Introduction

A chronic wound is a loss of skin or other tissues that do not heal during the time normally needed to heal others wounds. Treatment of these wounds can be long-lasting, requires specific medical skills and constitute a great challenge for contemporary medicine. The problem affects an estimated twenty million people around the world. This number may significantly increase due to ageing population and escalating incidence of civilization diseases such as obesity and diabetes (Bumpus and Maier, 2013). Globally, by 2020 the wound care market is projected to surpass 22 billion USD per year (Tricco et al., 2015). Impaired wound healing increases the number of operative procedures, lengthens hospital stays and worsens a patient's susceptibility to infection (Butler et al., 2010). Thus, many scientists focus on determining different factors affecting the process of wound healing, among others those related to the use of certain drugs, improper diet and exposure to environmental pollution. It is also possible to identify specific diseases that increase the risk of developing non-healing ulcers and to determine the effect of hypoxia on the healing process (Burns et al., 2003).

The methods that are currently used in the treatment of chronic wounds are multifactorial and include several steps. First and foremost, direct causes are sought that have made the treatment process difficult and attempts are being made to eliminate them. If, despite this, healing is still very slow or does not progress, the specific methods are used to support the process. However, traditional wound care procedures using debridement, infection control and typical dressings have limited efficacy, especially for treatment of chronic wounds, which is still a challenging task for healthcare experts.

The development of biomedical engineering has increased the interest in working out new therapeutic approaches for wounds difficult to heal. These include for example gene therapy, cell therapy, biological dressings, growth factors delivery and engineered skin equivalents. Among these new treatment modalities, stem cell-based therapies have gained interest as a part of regenerative medicine.

Currently, a rising number of stem cell therapies has been tested in clinical and preclinical trials in the context of their impact on wound healing (Leavitt et al., 2016, Tsai et al., 2018). The use of stem cells in the treatment of chronic wounds is a novel approach that uses processes that naturally occur in wound healing such as the action of growth factors, stimulation of immune processes and regulation of the inflammatory process, as well as improving the blood supply to developing tissue, which speeds up epidermis growth (Kolle et al., 2013).

The aim of this review is to summarize mechanisms by which different stem cells influence wound healing process and to describe latest strategies used to improve their therapeutic potential in the context of non-healing wounds. Moreover, we will mention some clinical trials and experiments on animal models, that support the use of stem cells, especially mesenchymal stem cells (MSCs), in chronic wound treatment. Finally, we will discuss limits and benefits of stem cell therapy in comparison to traditional ones.

Section snippets

Adult stem cells related to wound healing process

Stem cells, due to their properties - differentiation into other cell types and the potential for unlimited proliferation - are one of the most popular issues of contemporary medicine and biological sciences. According to their ability to differentiate, they can be divided into toti-, pluri-, multi- and unipotent, while according to their source - into embryonic (isolated from the blastocyst), adult (isolated from the mature organism, also known as somatic stem cells) and obtained from the

Stem cells application in wound healing

In larger burns and chronic wounds, the number and function of stem cells may be impaired. For example, it was shown, that chronic wound environment inhibits ADSCs proliferation rate and changes expression of some genes crucial for wound healing in these cells (Koenen et al., 2015). Moreover, EPCs derived from diabetic patients (that often suffer from non-healing ulcers) demonstrated decreased adherence to human umbilical vein endothelial cells, impaired proliferation and less involvement in

Discussion

Human skin is the largest organ of the human body and its main function is to provide proper protection against external factors and the penetration of pathogens into the body. Its continuity is of the greatest importance and any damage may be a potential gateway to infection. Wounds created within the skin are the result of the impact of various damaging and irritating factors leading to disruption of the skin's continuity, while the process of their treatment is multistage and can be

Declaration of interest

None.

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