Abstract
Wound healing is a complex process with a linear development that involves many actors in a multistep timeline commonly divided into four stages: Hemostasis, inflammation, proliferation, and remodeling. Chronic non-healing wounds fail to progress beyond the inflammatory phase, thus precluding the next steps and, ultimately, wound repair. Many intrinsic or extrinsic factors may contribute to such an occurrence, including patient health conditions, age-related diseases, metabolic deficiencies, advanced age, mechanical pressure, and infections. Great interest is being focused on the adipose tissue-derived stem cell’s (ASC) paracrine activity for its potential therapeutic impact on chronic non-healing wounds. In this review, we summarize the results of in vitro and in vivo experimental studies on the pro-wound healing effects of ASC-secretome and/or extracellular vesicles (EVs). To define an overall picture of the available literature data, experimental conditions and applied methodologies are described as well as the in vitro and in vivo models chosen in the reported studies. Even if a comparative analysis of the results obtained by the different groups is challenging due to the large variability of experimental conditions, the available findings are undoubtedly encouraging and fully support the use of cell-free therapies for the treatment of chronic non-healing wounds.
Highlights
Chronic non-healing wounds represent a massive healthcare system problem due to the high incidence and prevalence rate as well as psycho-socio-economic costs [1,2,3]
The in vitro studies examined in the present review, aimed at demonstrating the accelerating effects of adipose tissue-derived stem cell (ASC)-CM or ASC-extracellular vesicles (EVs) on the wound healing process, were conducted mainly on cell lines or primary cultures of fibroblasts, keratinocytes, or endothelial cells
It is essential to carry out studies using a human serum or synthetic supplementation, which could be certified for good manufacturing practice (GMP) use of ASCs or their secretome for wound healing
Summary
Chronic non-healing wounds represent a massive healthcare system problem due to the high incidence and prevalence rate as well as psycho-socio-economic costs [1,2,3]. Several studies have revealed that the implantation time of ASCs is usually too short to have an effective impact [37] In this context, ASC paracrine activity, through the secretion of a plethora of bioactive factors, was suggested to have the most prominent therapeutic impact in several conditions, including wound healing [38,39,40,41,42]. ASC paracrine activity, through the secretion of a plethora of bioactive factors, was suggested to have the most prominent therapeutic impact in several conditions, including wound healing [38,39,40,41,42] In this scenario, the study of ASC-conditioned medium (ASC-CM) ( known as ASC-secretome) has opened the way for the development of new cell-free therapies for tissue repair and regeneration [43,44,45,46,47,48]. Several studies have focused on the potential effects of the paracrine activity of ASCs, with the purpose of defining new cell-free therapies for the treatment of chronic wounds
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