Haubner Frank, Muschter Dominique, Pohl Fabian, Schreml Stephan, Prantl Lukas, Gassner Holger G
Department of Otorhinolaryngology, Division of Facial Plastic Surgery, University Medical Center, Regensburg 93053, Germany.
Department of Radiotherapy, University Medical Center, Regensburg 93053, Germany.
Int J Mol Sci. 2015 Oct 29;16(11):25947-58. doi: 10.3390/ijms161125935.
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.
外照射似乎与细胞因子及其他细胞调节因子数量的增加有关。微循环受损和纤维化是放疗导致的典型长期损伤的例子。脂肪组织来源的干细胞（ASC）被认为可促进伤口愈合，但其在放疗所致伤口中的作用尚不清楚。将正常人成纤维细胞（NHF）与ASC共同培养，并给予2 - 12格雷（Gy）的外照射。通过qPCR在共培养物照射48小时后测定细胞增殖及基质金属蛋白酶（MMP1、MMP2和MMP13）的mRNA水平。此外，通过酶联免疫吸附测定（ELISA）测定基质金属蛋白酶组织抑制剂（TIMP1、TIMP2）。与未照射的对照组相比，NHF和ASC单培养物在外照射后细胞增殖减少。ASC与NHF的共培养显示外照射后细胞增殖的损伤减轻。外照射后NHF中MMP1和MMP13的基因表达降低。照射后的NHF中MMP2表达增加。在共培养环境中，MMP1和MMP2基因表达水平上调。照射后NHF及其与ASC的共培养物中TIMP1和TIMP2蛋白表达增加。ASC似乎能刺激NHF的细胞增殖，并在外照射后调节相关的可溶性介质和蛋白酶。
