Stem Cell Therapy in Chronic Cutaneous Wound Healing, A Review

Background: Skin is considered as the largest organ of the body, responsible of numerous vital functions, therefore management and treatment of its lesions is of crucial importance. The natural wound healing process involves several overlapping stages as inflammation, neovascularization and extracellular matrix formation leading to tissue remodeling and re-epithelialization. Different types of cells and various signaling factors as chemokines, cytokines, and growth factors collaborate in the process. Disrupted mentioned procedure in severe conditions, can lead to formation of non-healing aged wounds and abnormal scars. Current remedies for these kind of lesions included administration of growth factors and cytokines to boost angiogenesis, tissue formation, and modulating inflammation, as well as applicating profitable skin grafts. Hyperbaric oxygen (HBO2) therapy, is another current method but with limited effectiveness. Eventually regenerative medicine has created a new promising horizon for treatment of skin chronic ulcers by using stem cells (SCs). Material and Methods: This review is an attempt to summarize the enhancing role of stem cell therapies in healing cutaneous wounds which is prepared by searching up-to-date articles of top researchers among journals with high impact factor. Results: The skin has the ability of self-regenerating due to endogenous stem cells, mainly located in hair follicles and endothelium of capillaries which can participate in wounds healing too, yet can be impaired due to microenvironment changes or inadequate because of aging or in serious pathophysiologic conditions, such as diabetes, deep burns, chronic ulcers, and prolonged ischemic conditions in the extremities. Cellular therapy can be a promising approach by which exogenous stem cells will be transferred to wound bed by aid of an appropriate scaffold. SCs can participate in wound healing as a source of replacing cells as well as secreting different factors which lead to immunomoduation influences and accelerating cell proliferation and differentiation especially fibroblasts, also proceeding angiogenesis, augmentation of matrix components deposition e.g. collagen, and recruitment of some specific lineage to the wound site, such as endothelial stem cells and some lymphocytes. Several sources of obtaining SCs are available which will be discussed below and choosing the adequate safe population is the most challenging part. Embryonic Stem Cells (ESC) are capable of high self-renewal and differentiation to any type of cells, but their potential tumorigenesis risk and ethical issues should be considered.Another option can be Adult Mesenchymal Stem Cells (ASC) which has a more limited capacity comparing with ESC, however, at the site of the wound, they can interact with the environment and be differentiated into a variety of different cells. Among all of ASCs, Hematopoietic Stem Cells and Adipose-Derived Stem Cells are the most studied ones with promising consequences. The next alternate is induced Pluripotent Stem Cells (iPSCs), which is created by reprogramming adult differentiated cells, but their application needs further assessment for their safety and risk of mutagenesis. Another key participant to a successful therapy is the used scaffold for delivering SCs, various types of them can be enumerated, as biologic scaffolds, e.g. Human Amniotic Membrane, or bioengineered and synthetic ones made of compatible components. Different cell treating processes are done to modulate the SCs for a better consequence. To achieve a better understanding, many other endeavors are done too, as three-dimensional extracellular matrix establishment and simulation of micro environmental conditions of wound to study more detailed behaviors of the cells. Conclusion: Valuable efforts have been devoted into finding effective cures for chronic wounds by aid of stem cell therapies, but lots of researches should be done yet to deepen the knowledge about aged wounds and role of SCs in its healing. More studies are still needed to increase the overall safety and efficacy of stem cell transplantation. selection the proper source of SCs, developing the processes of isolating, preparing, multiplying and transplanting SCs to the wound area are main practical challenges ahead. Considering importance of chronic wound treatment in health and appearances of patients, stem cell therapy should be supposed as a beneficial tool in spite of its high costs.

Keywords:

Stem Cell Therapy , Non-Healing Wounds , Chronic Ulcer , Regenerative Medicine