An older diabetes-induced mice model for studying skin wound healing

Abstract

Advances in wound treatment depend on the availability of animal models that reflect key aspects of human wound healing physiology. To this date, the accepted mouse models do not reflect defects in the healing process for chronic wounds that are associated with type two diabetic skin ulcers. The long term, systemic physiologic stress that occurs in middle aged or older Type 2 diabetes patients is difficult to simulate in preclinical animal model. We have strived to incorporate the essential elements of this stress in a manageable mouse model: long term metabolic stress from obesity to include the effects of middle age and thereafter onset of diabetes. At six-weeks age, male C57BL/6 mice were separated into groups fed a chow and High-Fat Diet for 0.5, 3, and 6 months. Treatment groups included long term, obesity stressed mice with induction of diabetes by streptozotocin at 5 months, and further physiologic evaluation at 8 months old. We show that this model results in a severe metabolic phenotype with insulin resistance and glucose intolerance associated with obesity and, more importantly, skin changes. The phenotype of this older age mouse model included a transcriptional signature of gene expression in skin that overlapped that observed with elderly patients who develop diabetic foot ulcers. We believe this unique old age phenotype contrasts with current mice models with induced diabetes.

Chronic Wound Healing Models

“…For example, if studying diabetic wound healing, the model animal should at least be representative of "middle age," with verification of long-term elevated blood glucose, metabolic changes, and biomarkers that demonstrate a correlation between the human disease state and recapitulate the chronicity associated with human nonhealing diabetic wounds. 179 Although further development of preclinical animal models will improve translatable innovations in wound therapeutics, recent advances in computer modeling and 3D models may provide better insight with the opportunity to manipulate the environment to more closely simulate the complex interactions between human skin cells, the immune response and the critical orchestration of the cytokine response. These models also allow for very highthroughput screening of potential therapeutic molecules which may then be tested directly in humans, bypassing the need for preclinical animal models.…”

Papel Da Coenzima Q10 Em Doenças Do Sistema Nervoso Central: Uma Mini Revisão

“…Modelo de diabetes induzida por dieta: Esse modelo envolve a administração de uma dieta rica em gordura ou rica em gordura e carboidratos por um período prolongado(LLABRE, 2022). A alimentação com alto teor calórico e inadequada pode levar à obesidade, resistência à insulina e desenvolvimento do DM tipo 2 em ratos(POBLETE-JARA, 2023). Esse modelo é 101 Além da teoria: contribuições das ciências fisiológicas para a saúde CAPÍTULO X utilizado para estudar os mecanismos subjacentes ao desenvolvimento do DM tipo 2 e avaliar intervenções terapêuticas (POBLETE-JARA, 2023).…”

Além da teoria: contribuições das ciências fisiológicas para a saúde

“…Modelo de diabetes induzida por dieta: Esse modelo envolve a administração de uma dieta rica em gordura ou rica em gordura e carboidratos por um período prolongado(LLABRE, 2022). A alimentação com alto teor calórico e inadequada pode levar à obesidade, resistência à insulina e desenvolvimento do DM tipo 2 em ratos(POBLETE-JARA, 2023). Esse modelo é 101 Além da teoria: contribuições das ciências fisiológicas para a saúde CAPÍTULO X utilizado para estudar os mecanismos subjacentes ao desenvolvimento do DM tipo 2 e avaliar intervenções terapêuticas (POBLETE-JARA, 2023).…”