Human Wounds and Its Burden: An Updated Compendium of Estimates

Sen, Chandan K.

doi:10.1089/wound.2019.0946

Cited by 681 publications

(530 citation statements)

References 116 publications

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“…Chronic DFUs are a serious life-threatening disease; they are rapidly increasing in incidence and often result in lower limb amputation and a shortened life span (2,(22)(23)(24). To date, treatments for DFUs remain limited and achieve modest efficacy in restoring healing (1).…”

Section: Discussionmentioning

confidence: 99%

Mevastatin promotes healing by targeting caveolin-1 to restore EGFR signaling

Sawaya¹,

Jozic²,

Stone³

et al. 2019

JCI Insight

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Section: Discussionmentioning

confidence: 99%

Mevastatin promotes healing by targeting caveolin-1 to restore EGFR signaling

Sawaya¹,

Jozic²,

Stone³

et al. 2019

JCI Insight

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“…This way, open wounds are a problem for 3% of the population older than 65 years of age in the USA. Besides, the USA Government estimates that the elderly population will be over 55 million by 2020, and thus, the number of chronic wounds is expected to grow (Sen, 2019). This represents a very important health expenditure for the national health systems of such countries.…”

Section: Skin Wound Healingmentioning

confidence: 99%

Extracellular Vesicles Derived From Mesenchymal Stem Cells (MSC) in Regenerative Medicine: Applications in Skin Wound Healing

Casado-Díaz

Quesada‐Gómez

Dorado

2020

Front. Bioeng. Biotechnol.

203

177

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The cells secrete extracellular vesicles (EV) that may have an endosomal origin, or from evaginations of the plasma membrane. The former are usually called exosomes, with sizes ranging from 50 to 100 nm. These EV contain a lipid bilayer associated to membrane proteins. Molecules such as nucleic acids (DNA, mRNA, miRNA, lncRNA, etc.) and proteins may be stored inside. The EV composition depends on the producer cell type and its physiological conditions. Through them, the cells modify their microenvironment and the behavior of neighboring cells. That is accomplished by transferring factors that modulate different metabolic and signaling pathways. Due to their properties, EV can be applied as a diagnostic and therapeutic tool in medicine. The mesenchymal stromal cells (MSC) have immunomodulatory properties and a high regenerative capacity. These features are linked to their paracrine activity and EV secretion. Therefore, research on exosomes produced by MSC has been intensified for use in cell-free regenerative medicine. In this area, the use of EV for the treatment of chronic skin ulcers (CSU) has been proposed. Such sores occur when normal healing does not resolve properly. That is usually due to excessive prolongation of the inflammatory phase. These ulcers are associated with aging and diseases, such as diabetes, so their prevalence is increasing with the one of such latter disease, mainly in developed countries. This has very important socio-economic repercussions. In this review, we show that the application of MSC-derived EV for the treatment of CSU has positive effects, including accelerating healing and decreasing scar formation. This is because the EV have immunosuppressive and immunomodulatory properties. Likewise, they have the ability to activate the angiogenesis, proliferation, migration, and differentiation of the main cell types involved in skin regeneration. They include endothelial cells, fibroblasts, and keratinocytes. Most of the studies carried out so far are preclinical. Therefore, there is a need to advance more in the knowledge about the conditions of production, isolation, and action mechanisms of EV. Interestingly, their potential application in the treatment of CSU opens the door for the design of new highly effective therapeutic strategies.

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“…Chronic wound patients have a reduced ability to undergo normal tissue repair and are more susceptible to ulcers, resulting in patient trauma, and often the need for limb amputation [1,2]. At present, chronic wounds impact four million Europeans per year, and at least 1% of people living in high economy countries will experience a complex wound in their lifetime [3,4]. Existing therapies for chronic wounds are expensive, and approximately 2-4% of the total European health budget is being spent on wound care [5].…”

Section: Introductionmentioning

confidence: 99%

Can supernatant from immortalized adipose tissue MSC replace cell therapy? An in vitro study in chronic wounds model

et al. 2020

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Background: Mesenchymal stem cells (MSCs) secrete a cocktail of growth factors and cytokines, which could promote tissue regeneration and wound healing. Therefore, in clinical practice, post-culture MSC supernatant treatment could be a more attractive alternative to autologous stem cell transplantation. In this study, we compared the regenerative properties of supernatants harvested from four newly established human adipose tissue mesenchymal stem cell lines (HATMSCs) derived from chronic wound patients or healthy donors. Methods: HATMSC supernatants were produced in a serum-free medium under hypoxia and their content was analyzed by a human angiogenesis antibody array. The regenerative effect of HATMSCs supernatants was investigated in an in vitro model of chronic wound, where cells originating from human skin, such as microvascular endothelial cells (HSkMEC.2), keratinocytes (HaCaT), and fibroblasts (MSU-1.1), were cultured in serum-free and oxygen-reduced conditions. The effect of supernatant treatment was evaluated using an MTT assay and light microscopy. In addition, fibroblasts and HATMSCs were labeled with PKH67 and PKH26 dye, respectively, and the effect of supernatant treatment was compared to that obtained when fibroblasts and HATMSCs were co-cultured, using flow cytometry and fluorescent microscopy. Results: A wide panel of angiogenesis-associated cytokines such as angiogenin, growth-regulated oncogene (GRO), interleukin-6 and 8 (IL-6, IL-8), vascular endothelial growth factor (VEGF), insulin growth factor 1 (IGF-1), and matrix metalloproteinase (MMP) were found in all tested HATMSCs supernatants. Moreover, supernatant treatment significantly enhanced the survival of fibroblasts, endothelial cells, and keratinocytes in our chronic wound model in vitro. Importantly, we have shown that in in vitro settings, HATMSC supernatant treatment results in superior fibroblast proliferation than in the case of co-culture with HATMSCs. Conclusions: Our results suggest that therapy based on bioactive factors released by the immortalized atMSC into supernatant has important effect on skin-derived cell proliferation and might preclude the need for a more expensive and difficult cell therapy approach to improve chronic wound healing.

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Human Wounds and Its Burden: An Updated Compendium of Estimates

Cited by 681 publications

References 116 publications

Mevastatin promotes healing by targeting caveolin-1 to restore EGFR signaling

Mevastatin promotes healing by targeting caveolin-1 to restore EGFR signaling

Extracellular Vesicles Derived From Mesenchymal Stem Cells (MSC) in Regenerative Medicine: Applications in Skin Wound Healing

Can supernatant from immortalized adipose tissue MSC replace cell therapy? An in vitro study in chronic wounds model

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