Abstract
Severe burns induce a prolonged inflammatory response in subcutaneous adipose tissue that modulates signaling in adipose-derived stem cells (ASCs), which hold potential for healing burn wounds or generating skin substitutes. Using a 60% rat scald burn model, we conducted a series of experiments to determine which cells isolated from the adipose tissue produced inflammatory mediators and how these changes affect ASC fate and function. The stromal vascular fraction (SVF), adipocytes, and ASCs were isolated from adipose tissue at varying times up to 4 weeks postburn and from non-injured controls. Endpoints included inflammatory marker expression, expression of ASC-specific cell-surface markers, DNA damage, differentiation potential, and proliferation. Inflammatory marker expression was induced in adipocytes and the SVF at 24 and 48 h postburn; expression of inflammatory marker mRNA transcripts and protein returned to normal in the SVF isolated 1 week postburn. In enriched ASCs, burns did not alter cell-surface expression of stem cell markers, markers of inflammation, differentiation potential, or proliferative ability. These results suggest that adipocytes and the SVF produce large quantities of inflammatory mediators, but that ASCs do not, after burns and that ASCs are unaffected by burn injury or culturing procedures.. They also suggest that cells isolated over 48 h after injury are best for cell culture or tissue engineering purposes.
Highlights
In 2013 alone, 35 million burn injuries were reported worldwide and resulted in approximately 2.9 million hospitalizations and 238,000 deaths [1, 2]
Stem cells isolated from adipose tissue are similar to bone marrow-derived mesenchymal stem cells (MSCs) in that adipose-derived stem cells (ASCs) can differentiate into many cell types including chondrocytes, osteoblasts, adipocytes, cardiomyocytes, endothelial cells, epithelium, and neuronal cells
We have shown that post-burn inflammation in the adipose tissue is mediated by the adipocytes and the stromal vascular fraction (SVF)
Summary
In 2013 alone, 35 million burn injuries were reported worldwide and resulted in approximately 2.9 million hospitalizations and 238,000 deaths [1, 2]. It is relatively easy to isolate up to 5000 ASCs from one gram of adipose tissue [3,4,5] Aside from their ability to differentiate into a variety of cell types, ASCs secrete an abundance of cytokines and growth factors, including interleukin (IL)-6, IL-7, IL-8, IL-11, IL-12, fibroblast growth factor, epidermal growth factor, keratinocyte growth factor, and macrophage colony-stimulating factor [6, 7]. The production of these factors may account for the therapeutic effect of ASCs in wound healing [8, 9], tissue regeneration [10], angiogenesis [11], and immunomodulation [9]
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