Clinical value of adipose tissue-derived stem cells application in healing of experimental diabetic and nondiabetic burn

Abstract

Burns occur with high incidence worldwide causing high mortality and morbidity. [1] After skin injury, the skin depends on stem cells for its renewal involving inflammation, angiogenesis with cytokines, and growth factors production. [2] In pathological conditions as diabetes mellitus, healing is not completed or delayed. Chronic nonhealing burns have many precipitating factors as reduced angiogenesis and impairment in the cytokines production. [3] In diabetes, the adult stem cell cannot function properly resulting in impaired healing. [4] Adipose-derived stromal cells (ADSCs) treatments have been associated with promising outcomes in the wound healing. [5] Serpin B3, also known as "squamous cell carcinoma antigen-1", is a member of the serpin superfamily of serine protease inhibitors which are involved in the regulation of apoptosis, inflammation, and angiogenesis. [6] Keratinocyte growth factor-1 (KGF-1) is a member of the fibroblast growth factor family produced by fibroblasts, smooth muscle cells, and endothelial cells. [7] It is expressed in injured skin and extensively produced in the early healing process of the wound. [8] KGF-1 has been shown to induce migration and multiplication of keratinocytes that produce various growth factors and cytokines during the healing process. [9,10] Therefore, identification of the value and possible adverse effects of ADSCs for burn healing in normal and diabetic conditions using an animal model are needed before the human trials. The assessment of healing by Serpin B3 and KGF-1 as novel biomarkers and molecular targets of impaired diabetic wound healing. Objectives:The mechanisms underlying delayed healing in diabetes are not completely understood and biomarkers to identify and to treat such pathways are needed. The aim of the present study is to assess the clinical effect of adipose tissue-derived stem cells in accelerating third-degree burns healing in diabetic and normal mouse model and to restore skin integrity. Assessment of healing by Serpin B3 and keratinocyte growth factor-1 (KGF-1) as novel biomarkers and possible molecular targets of impaired diabetic wound healing. Materials and Methods: Forty male mice were set up as an experimental model for third-degree burn. They were randomly divided into four groups as follows: the control group, the diabetic (received high-fat diet) burnt group, the diabetic burnt group treated with adipose tissue-derived stem cells, and the nondiabetic burnt group treated with adipose tissue-derived stem cells. The rate of burn healing, the degree of angiogenesis, and collagen formation were evaluated by histological examination, Serpin B3 (enzyme-linked immunosorbent assay), and KGF-1 measured by real-time polymerase chain reaction. They were sacrificed after the 3 rd week for tissue sampling. Results: Adipose tissue-derived stem cells accelerate the healing of experimental burns. Serpin B3 was upregulated in adipose tissue-derived stem cells treated burns associated with denser collagen deposition, angiogenesis, and increased expressi...

Perimatrix of middle ear cholesteatoma: A granulation tissue with a specific transcriptomic signature

“…The effects of downregulated endopeptidase inhibitors in the cholesteatoma perimatrix compared to COM without cholesteatoma should be further investigated. For example, higher levels of serpin B3 were detected in successful healing that can differentiate between pathogenic and nonpathogenic burn healing in diabetic mice . The downregulation of this serpin could potentially promote the processes of pathogenic healing in cholesteatoma perimatrix as well.…”