Center for Translational Research in Biomedical Sciences, Liver Transplantation Program and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Niao-Sung, Kaohsiung, Taiwan.
J Cell Physiol. 2012 Oct;227(10):3417-25. doi: 10.1002/jcp.24042.
Adipose-derived stem cells (ASCs) are of great interest for the development of novel cell therapies due to their ease of isolation and expansion, immunosuppressive activity, and multilineage differentiation potential. However, the mechanisms underlying the therapeutic potential of ASCs remain to be elucidated. Others and we have shown that nuclear proteins such as histone H1 and high mobility group box 1 (HMGB1) play important roles in the maturation of dendritic cells (DCs). Furthermore, we previously demonstrated translocation of histone H1 from the nucleus to the cytoplasm and activation of mitogen-activated protein kinases (MAPKs) in DCs. In the present study, we confirmed that histone H1 does not alter the immunophenotype and immunosuppression potential of ASCs, but that histone H1 enhanced wound healing and increased interleukin (IL)-6 expression. Moreover, histone H1 treated-ASCs showed up-regulation of MAPKs extracellular-regulated kinase 1/2 (ERK1/2) and sequential NF-κB translocation. Finally, we found that culture in differentiation media supplemented with histone H1 enhanced ASC osteogenesis. In contrast, inhibition of histone H1 by small interfering RNA (siRNA) reduced osteogenic differentiation markers including ALP. These results suggest that histone H1 may be useful for induction of mesenchymal stem cells in tissue engineering and future potential ASC therapies.
脂肪来源的干细胞（ASCs）由于其易于分离和扩增、免疫抑制活性和多能分化潜力，因此对于新型细胞治疗的发展具有重要意义。然而，ASCs 的治疗潜力的机制仍有待阐明。其他人已经表明，核蛋白如组蛋白 H1 和高迁移率族蛋白 B1（HMGB1）在树突状细胞（DC）的成熟中发挥重要作用。此外，我们之前证明了组蛋白 H1 从细胞核向细胞质的易位以及 DC 中丝裂原活化蛋白激酶（MAPKs）的激活。在本研究中，我们证实组蛋白 H1 不会改变 ASC 的免疫表型和免疫抑制潜力，但组蛋白 H1 增强了伤口愈合并增加了白细胞介素（IL）-6 的表达。此外，组蛋白 H1 处理的 ASC 表现出 MAPKs 细胞外调节激酶 1/2（ERK1/2）和顺序 NF-κB 易位的上调。最后，我们发现，在补充有组蛋白 H1 的分化培养基中培养可增强 ASC 的成骨作用。相比之下，通过小干扰 RNA（siRNA）抑制组蛋白 H1 会降低成骨分化标志物，包括碱性磷酸酶（ALP）。这些结果表明，组蛋白 H1 可能有助于诱导组织工程中的间充质干细胞和未来潜在的 ASC 治疗。
