TY - BOOK

T1 - The effects of EPO on cutaneous wound healing, dermal stem cell marker activation, and gene expression patterns

AU - Fathi, Meimanat

N1 - Doctoral thesis

PY - 2023

Y1 - 2023

N2 - Scars often have a negative impact on an individual’s self-perception of beauty, quality of life, and self-confidence. In order to reduce these negative impacts, researchers are attempting to better understand the biological mechanisms that lead to scar formation, so that more effective clinical treatments can be developed. A long-term goal is to accelerate skin regeneration and facilitate scarless healing of wound injuries. In previous studies, researchers have shown that low dose erythropoietin (EPO) has regenerative and cytoprotective effects in preclinical animal models, and even in clinical patients presenting with burns or diabetic wounds. However, the molecular mechanisms through which EPO affects scar formation and/or wound healing in human skin tissue remains unclear. Therefore, in this research project, the effect of EPO on skin-graft donor site wound healing in human patients is evaluated using immunohistochemical methods, and then additional in vitro experiments are conducted to test how the effects of EPO may be impacted by the presence of other small molecules called pro-inflammatory cytokines. Specifically, in one study: (i) the effect of systemic application of EPO on immunohistochemical indicators of wound healing is tested using skin samples from a clinical trial that compared EPO-treated to placebo-treated groups. In a second in vitro study: (ii) the effect of EPO administration (alone and in combination with different cytokines, e.g., IL-6, TNF-α) on expression levels of genes linked to wound healing was tested. In the first study, immunohistochemical analyses failed to uncover any strong patterns that differentiated treatment and control groups, with the exception of von Willebrand factor, which showed signs of decreased expression in the EPO-treated group. In the second study, EPO administration, and co-administration of EPO with TNF-α and IL-6 cytokines, led to some changes in gene expression levels in foreskin-derived mesenchymal stem cells. However, treatment with EPO alone, and co-administration of EPO with TNF-α and IL-6, did not lead to statistically significant differences in GO or KEGG signaling pathways.

AB - Scars often have a negative impact on an individual’s self-perception of beauty, quality of life, and self-confidence. In order to reduce these negative impacts, researchers are attempting to better understand the biological mechanisms that lead to scar formation, so that more effective clinical treatments can be developed. A long-term goal is to accelerate skin regeneration and facilitate scarless healing of wound injuries. In previous studies, researchers have shown that low dose erythropoietin (EPO) has regenerative and cytoprotective effects in preclinical animal models, and even in clinical patients presenting with burns or diabetic wounds. However, the molecular mechanisms through which EPO affects scar formation and/or wound healing in human skin tissue remains unclear. Therefore, in this research project, the effect of EPO on skin-graft donor site wound healing in human patients is evaluated using immunohistochemical methods, and then additional in vitro experiments are conducted to test how the effects of EPO may be impacted by the presence of other small molecules called pro-inflammatory cytokines. Specifically, in one study: (i) the effect of systemic application of EPO on immunohistochemical indicators of wound healing is tested using skin samples from a clinical trial that compared EPO-treated to placebo-treated groups. In a second in vitro study: (ii) the effect of EPO administration (alone and in combination with different cytokines, e.g., IL-6, TNF-α) on expression levels of genes linked to wound healing was tested. In the first study, immunohistochemical analyses failed to uncover any strong patterns that differentiated treatment and control groups, with the exception of von Willebrand factor, which showed signs of decreased expression in the EPO-treated group. In the second study, EPO administration, and co-administration of EPO with TNF-α and IL-6 cytokines, led to some changes in gene expression levels in foreskin-derived mesenchymal stem cells. However, treatment with EPO alone, and co-administration of EPO with TNF-α and IL-6, did not lead to statistically significant differences in GO or KEGG signaling pathways.

U2 - 10.15488/13329

DO - 10.15488/13329

M3 - Doctoral thesis

CY - Hannover

ER -