Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Department of Otorhinolaryngology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Stem Cell Rev Rep. 2017 Apr;13(2):267-277. doi: 10.1007/s12015-017-9719-3.
Adipose tissue-derived stem cells (ASCs) are known to be able to promote repair of injured tissue via paracrine factors. However, the effect of cell density and inflammatory cytokines on the paracrine ability of ASCs remains largely unknown. To investigate these effects, ASCs were cultured in 8000 cells/cm, 20,000 cells/cm, 50,000 cells/cm, and 400,000 cells/cm with and without 10 or 20 ng/ml tumor necrosis factor alpha (TNFα) and 25 or 50 ng/ml interferon gamma (IFNγ). ASC-sheets formed at 400,000 cells/cm after 48 h of culture. With increasing concentrations of TNFα and IFNγ, ASC-sheets with 400,000 cells/cm had increased production of angiogenic factors Vascular Endothelial Growth Factor and Fibroblast Growth Factor and decreased expression of pro-inflammatory genes TNFA and Prostaglandin Synthase 2 (PTGS2) compared to lower density ASCs. Moreover, the conditioned medium of ASC-sheets with 400,000 cells/cm stimulated with the low concentration of TNFα and IFNγ enhanced endothelial cell proliferation and fibroblast migration. These results suggest that a high cell density enhances ASC paracrine function might beneficial for wound repair, especially in pro-inflammatory conditions.
脂肪组织来源的干细胞 (ASCs) 已知能够通过旁分泌因子促进受损组织的修复。然而，细胞密度和炎症细胞因子对 ASCs 的旁分泌能力的影响在很大程度上仍不清楚。为了研究这些影响，将 ASCs 在 8000 个细胞/cm、20000 个细胞/cm、50000 个细胞/cm 和 400000 个细胞/cm 培养，分别有无 10 或 20ng/ml 肿瘤坏死因子 alpha (TNFα) 和 25 或 50ng/ml 干扰素 gamma (IFNγ)。在培养 48 小时后，在 400000 个细胞/cm 处形成 ASC 薄片。随着 TNFα 和 IFNγ 浓度的增加，与低密度 ASCs 相比，400000 个细胞/cm 的 ASC 薄片产生更多的血管生成因子血管内皮生长因子和成纤维细胞生长因子，并且促炎基因 TNFA 和前列腺素合成酶 2 (PTGS2) 的表达降低。此外，用低浓度 TNFα 和 IFNγ 刺激的 400000 个细胞/cm 的 ASC 薄片的条件培养基增强了内皮细胞增殖和成纤维细胞迁移。这些结果表明，高细胞密度增强 ASC 旁分泌功能可能有益于伤口修复，特别是在炎症条件下。
