Department of Advanced Biomedical Sciences, University of Naples "Federico II", Naples, Italy.
Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy.
J Cell Physiol. 2018 Aug;233(8):6241-6249. doi: 10.1002/jcp.26493. Epub 2018 Mar 1.
Sheep is a relevant large animal model that is frequently used to test innovative tissue engineering (TE) approaches especially for bone reconstruction. Mesenchymal stem cells (MSCs) are used in TE applications because they represent key component of adult tissue repair. Importantly, MSCs from different species show similar characteristics, which facilitated their application in translational studies using animal models. Nowadays, many researches are focusing on the use of ovine mesenchymal stem cells (oMSCs) in orthopedic preclinical settings for regenerative medicine purposes. Therefore, there is a need to amplify our knowledge on the mechanisms underlying the behaviour of these cells. Recently, several studies have shown that MSC function is largely dependent on factors that MSCs release in the environment, as well as, in conditioned medium (CM). It has been demonstrated that MSCs through autocrine and paracrine signals are able to stimulate proliferation, migration, and differentiation of different type of cells including themselves. In this study, we investigated the effects of the CM produced by oMSCs on oMSCs themselves and we explored the signal pathways involved. We observed that CM caused an enhancement of oMSC migration. Furthermore, we found that CM increased levels of two membrane proteins involved in cell migration, Aquaporin 1 (AQP1), and C-X-C chemokine receptor type 4 (CXCR4), and activated Akt and Erk intracellular signal pathways. In conclusion, taken together our results suggest the high potential of autologous CM as a promising tool to modulate behaviour of MSCs thus improving their use in therapeutically approaches.
绵羊是一种常用于测试创新组织工程（TE）方法的相关大型动物模型，特别是用于骨重建。间充质干细胞（MSCs）被用于 TE 应用，因为它们是成人组织修复的关键组成部分。重要的是，来自不同物种的 MSCs 表现出相似的特征，这促进了它们在使用动物模型的转化研究中的应用。如今，许多研究都集中在使用绵羊间充质干细胞（oMSCs）在骨科临床前环境中用于再生医学目的。因此，需要加深我们对这些细胞行为背后机制的了解。最近，几项研究表明，MSC 的功能在很大程度上取决于 MSC 在环境中释放的因子，以及条件培养基（CM）中的因子。已经证明，MSC 通过自分泌和旁分泌信号能够刺激包括自身在内的不同类型细胞的增殖、迁移和分化。在这项研究中，我们研究了 oMSCs 产生的 CM 对 oMSCs 本身的影响，并探索了涉及的信号通路。我们观察到 CM 引起 oMSC 迁移的增强。此外，我们发现 CM 增加了两种参与细胞迁移的膜蛋白的水平，水通道蛋白 1（AQP1）和 C-X-C 趋化因子受体 4（CXCR4），并激活了 Akt 和 Erk 细胞内信号通路。总之，我们的研究结果表明，自体 CM 作为一种有前途的调节 MSC 行为的工具具有很大的潜力，从而提高了它们在治疗方法中的应用。
