Exogenous metabolic stimulators mitigate the negative effects of glycemia on fibroblast metabolism and proliferation

Talbert, Alyssa Jane (2019) Exogenous metabolic stimulators mitigate the negative effects of glycemia on fibroblast metabolism and proliferation. Masters thesis, Northern Arizona University.

Text Talbert_2019_Exogenous_metabolic_stimulators_glycemia_fibroblast.pdf - Published Version Restricted to Repository staff only Download (24MB) | Request a copy

Abstract

Diabetes Mellitus currently affects 30.3 million people in the United States and 422 million worldwide. When diabetes is uncontrolled there are a host of accompanying systemic diseases and complications, one common complication is the development of chronic non-healing diabetic foot ulcers. Many therapies are currently available to aid in the healing of these chronic wounds; however, not all therapies are successful for all wounds. Growth factor and cytokine injections are a commercially available and novel therapy, which are used to treat non-healing diabetic foot ulcers. The use of growth factor and cytokine injections has shown promise in some patients clinically, however the results of a few clinical studies have demonstrated variable effects. Therefore, further investigation into the effects that exogenous metabolic stimulators (e.g. growth factors and cytokines) have on specific aspects of wound healing may provide new insights into the usefulness of these compounds in this clinical context. This study demonstrated that exposing human dermal fibroblast neonatal (hDFn) cells to hyperglycemic conditions to mimic diabetic conditions results in altered cell morphology, decreased proliferation, and decreased metabolic activity compared to hDFn cells grown in hypoglycemic and normal glycemic conditions. Addition of an exogenous metabolic stimulator (EMS) which contains growth factors such as receptor tyrosine kinase erbb2 (Erbb2) and epidermal growth factor receptor (EGFR) demonstrated the ability to mitigate the negative effects caused by hyperglycemia. The positive effects observed from the addition of exogenous metabolic stimulators may be due to the signaling of proliferation cascades from Erbb2 and EGFR. We found that the exogenous metabolic stimulator (Axolotl Ambient, AA05) used in this study has the ability to increase proliferation, increase metabolic activity, and alter cell morphology for hDFn cells grown in hyperglycemic conditions towards morphology similar to that of a myofibroblast. The results observed in this study suggest that in an uncontrolled hyperglycemic diabetic patient, the use of an exogenous metabolic stimulator may help to aid in wound healing by stimulating an increase in proliferation and metabolic activity of hDFn cells to help facilitate wound closure.

Item Type:	Thesis (Masters)
Publisher’s Statement:	© Copyright is held by the author. Digital access to this material is made possible by the Cline Library, Northern Arizona University. Further transmission, reproduction or presentation of protected items is prohibited except with permission of the author.
Keywords:	Cytokines; DFU's; Diabetes; Growth Factors; hDFn; Wound Healing; Hypoglycemia
Subjects:	Q Science > QP Physiology
MeSH Subjects:	C Diseases > C06 Digestive System Diseases C Diseases > C26 Wounds and Injuries
NAU Depositing Author Academic Status:	Student
Department/Unit:	Graduate College > Theses and Dissertations College of the Environment, Forestry, and Natural Sciences > Biological Sciences
Date Deposited:	31 Jan 2022 18:00
Last Modified:	31 Jan 2022 18:00
URI:	https://openknowledge.nau.edu/id/eprint/5606

Actions (login required)

IR Staff Record View

Downloads