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Creation and Transplantation of an Adipose-derived Stem Cell ASC Sheet in a Diabetic Wound-healing Model
Published on: August 4, 2017
Renal dysfunction aggravated impaired cutaneous wound healing in diabetic mice
Ping Xie1, Mimi Wu Young1, Huining Bian1
1Division of Plastic and Reconstructive Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Abstract:
Renal dysfunction has been associated with poor outcomes of wound healing in the diabetic population. The purpose of this study was to create an excisional wound healing model in diabetic mice with renal dysfunction to investigate the combined effects of diabetes and nephropathy on cutaneous ulcers. Renal impairment was introduced in diabetic db/db mice through unilateral nephrectomy and electrocoagulation of the contralateral kidney. Renal function was subsequently monitored with assays of blood urea nitrogen and spot urinary protein/creatinine ratio. After 8 weeks, splinted, full-thickness excisional wounds were created on the dorsal skin and harvested on postoperative days 7 and 14 for further evaluation of wound healing. Renal injury promoted the increase of blood urea nitrogen 3 weeks after initial operation, which was maintained at double the control level throughout the study, concomitantly leading to a significant increase of spot urinary protein excretion. Diabetic mice with renal injury displayed notably impaired wound healing processes, concurrent with reductions in cellular proliferation and angiogenesis, as well as increases in M1 polarized macrophages, infiltrated neutrophils, oxidative stress, and cellular apoptosis. Furthermore, quantitative polymerase chain reaction (qPCR) results displayed corresponding changes of related genes (TNF-α, IL-1β, SOD2) in the wounds of renal injured db/db mice. Renal manipulation in this study accelerated the progress of renal impairment, which was demonstrated to aggravate impaired cutaneous wound healing in diabetic mice.
Insights
Diabetic mice with kidney dysfunction showed significantly worse wound healing. This impaired healing involved reduced cell growth and blood vessel formation, and increased inflammation and cell death.
Area of Science:
- Nephrology
- Diabetology
- Wound Healing Research
Background:
- Renal dysfunction is linked to poor wound healing in diabetic patients.
- Diabetes mellitus complicates wound repair, and co-existing kidney disease may exacerbate this.
- Understanding the interplay between diabetes, nephropathy, and cutaneous wound healing is crucial.
Purpose of the Study:
- To establish a murine model of diabetic nephropathy for studying cutaneous ulcer healing.
- To investigate the combined impact of diabetes and induced renal dysfunction on wound repair.
- To analyze the cellular and molecular mechanisms underlying impaired wound healing in this model.
Main Methods:
- Diabetic db/db mice underwent unilateral nephrectomy and contralateral kidney electrocoagulation to induce renal impairment.
- Renal function was assessed via blood urea nitrogen and urinary protein/creatinine ratio.
- Excisional wounds were created and analyzed at 7 and 14 days post-operation for healing parameters.
Main Results:
- Induced renal injury significantly elevated blood urea nitrogen and urinary protein levels in diabetic mice.
- Diabetic mice with renal injury exhibited markedly impaired wound healing.
- This impairment was characterized by decreased cellular proliferation, reduced angiogenesis, increased M1 macrophages, neutrophil infiltration, oxidative stress, and apoptosis.
Conclusions:
- The developed model effectively demonstrates that renal dysfunction exacerbates impaired cutaneous wound healing in diabetic mice.
- Key molecular changes in wounds include altered expression of TNF-α, IL-1β, and SOD2.
- These findings highlight the critical role of kidney health in managing diabetic wound complications.
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