Function and Therapeutic Potential of Mesenchymal Stem Cells and Their Acellular Derivatives on Non-Healing Chronic Skin Ulcers

Abstract

Non-healing chronic skin ulcers are considered a major biological, psychological, and financial burden for both patients and health systems. Multidisciplinary endeavors are required to address this refractory disease, in order to find definitive solutions that lead to improved living conditions. Diabetes, venous stasis, arterial insufficiency, pressure and radiation are common risk factors associated with chronic wounds. Unfortunately, the cured state for these wounds has a high relapse rate, which adversely affects the patient's quality of life. Nevertheless, advances on regenerative medicine have allowed the development of cell-based therapies that promote wound healing by increasing cell migration and differentiation. Particularly, mesenchymal stem cells (MSCs) and their acellular derivatives have emerged as an attractive therapeutic agent in various diseases, including chronic skin ulcers, due to their role in immunomodulation and tissue regeneration. In this review discusses the characteristics of MSCs as well as their regenerative properties and their action mechanisms on wound healing. Finally, the perspectives of MSCs and their acellular derivatives in clinical chronic skin ulcer therapy are also explored.

Current Status and Future Prospects of Genome-Scale Metabolic Modeling to Optimize the Use of Mesenchymal Stem Cells in Regenerative Medicine

“…It combines the knowledge and application of various fields such as tissue engineering, cell transplantation, stem cell biology, biomechanics, prosthetics, nanotechnology, and biochemistry to replace or restore human cells, tissues, or organs to their normal functions (Sampogna et al, 2015). A variety of regenerative medicine therapies are available (see Lonner et al, 2000;Blais et al, 2013;Zhang X. et al, 2013;Trushina and Mielke, 2014;Björnson et al, 2016;Moreira et al, 2017), but their success has been limited by functional obstacles that increase the risk of harm to patients and reduce their efficacy as a therapeutic (Neman et al, 2012;Campana et al, 2014;Goldberg et al, 2017;Cunningham et al, 2018;Solarte et al, 2018). Despite recent progress, there is obvious room for improvements regarding both the safety and efficacy of therapies for patients.…”

“…In many therapeutic contexts, it is now recognized that MSCs exert their healing effects through paracrine signaling and cell-to-cell contact, not by replacing cells (Fitzsimmons et al, 2018). There are a few notable examples using hSMCs as paracrine-mediated treatment currently in development (Amorin et al, 2014;Hofer and Tuan, 2016;Archambault et al, 2017;Moreira et al, 2017;Cunningham et al, 2018;Ibraheim et al, 2018;Solarte et al, 2018). The reported success of these studies indicates that the MSC secretome exerts beneficial effects that may be exploited by therapeutic applications.…”

“…These models can provide insight into the metabolic functions of possible interacting organisms or the various cell types residing within the same organism (Levy and Borenstein, 2013;Dougherty et al, 2017). Given that hMSCs are intended to be integrated into a host system for clinical application (Han et al, 2012;Levy and Borenstein, 2013;Burke et al, 2016;Archambault et al, 2017;Goldberg et al, 2017;Moreira et al, 2017;Cunningham et al, 2018;Hu et al, 2018;Ibraheim et al, 2018;Solarte et al, 2018), this could provide useful insights.…”

“…In recent years, there has been increasing interest in the possibilities offered by regenerative medicine (Maienschein, 2011;Sampogna et al, 2015), a field which seeks solutions for the restoration of the structure and functions of organs and tissues that have become permanently damaged. While regenerative medicine has enjoyed success in some areas, treatment can result in danger to patients or in therapeutic inefficiency (Neman et al, 2012;Campana et al, 2014;Goldberg et al, 2017;Moreira et al, 2017;Cunningham et al, 2018;Solarte et al, 2018) that have pushed researchers to continuously search for novel approaches to address limitations.…”