Abstract
External radiation seems to be associated with increased amounts of cytokines and other cellular modulators. Impaired microcirculation and fibrosis are examples of typical long term damage caused by radiotherapy. Adipose tissue-derived stem cells (ASC) are discussed to enhance wound healing, but their role in wounds due to radiotherapy is poorly understood. Normal human fibroblasts (NHF) and ASCs were co-cultured and external radiation with doses from 2–12 Gray (Gy) was delivered. Cell proliferation and mRNA levels of matrix metalloproteinases (MMP1, MMP2 and MMP13) were determined 48 h after irradiation of the co-cultures by qPCR. Additionally, tissue inhibitors of matrix metalloproteinases (TIMP1, TIMP2) were determined by enzyme-linked immunosorbent assay (ELISA). There was a reduction of cell proliferation after external radiation in mono-cultures of NHFs and ASCs compared to controls without irradiation. The co-culture of ASCs and NHFs showed reduced impairment of cell proliferation after external radiation. Gene expression of MMP1 and MMP13 was reduced after external irradiation in NHF. MMP2 expression of irradiated NHFs was increased. In the co-culture setting, MMP1 and MMP2 gene expression levels were upregulated. TIMP1 and TIMP2 protein expression was increased after irradiation in NHFs and their co-cultures with ASCs. ASCs seem to stimulate cell proliferation of NHFs and modulate relevant soluble mediators as well as proteinases after external radiation.
Highlights
Preoperative radiotherapy is a well-documented risk factor for postsurgical complications [1]
That is why we evaluated the effects of external radiation on normal human fibroblasts (NHF) and the effects of adipose-derived stem cells (ASC) in a co-culture setting with respect to matrix metalloproteinases (MMP) und TIMPs
External radiation resulted in a decreased cell proliferation of Normal human fibroblasts (NHF)
Summary
Preoperative radiotherapy is a well-documented risk factor for postsurgical complications [1]. Wound healing represents a complex interaction of cells, cytokines, chemokines and various extracellular matrix proteins. In previous experiments with human dermal microvascular endothelial cells (HDMEC), we detected elevated concentrations of pro-inflammatory mediator molecules (cytokines/chemokines) in irradiated cell culture supernatants. Dermal fibroblasts are responsible for the correct deposition and remodeling of collagen bundles After external radiation, these cells seem to generate a disorganized network of collagen fibers. MMP and TIMP coordinate extracellular matrix production and seem to be essential during the inflammatory phase of wound healing [16,17,18]. That is why we evaluated the effects of external radiation on normal human fibroblasts (NHF) and the effects of adipose-derived stem cells (ASC) in a co-culture setting with respect to MMPs und TIMPs
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