Department of Oncology, Biology and Genetics, University of Genoa, Largo Rosanna Benzi 10, 16132 Genova, Italy.
Biomaterials. 2011 May;32(15):3689-99. doi: 10.1016/j.biomaterials.2011.01.071. Epub 2011 Mar 2.
Most urgent health problems are related to a blood vessel formation failure. The use of stem cells from different sources or species for both in vitro and in vivo engineering of endothelium does not necessarily imply their direct commitment towards a vascular phenotype. In the present study, we used human amniotic fluid stem cells (AFSC) to evoke a strong angiogenic response in murine recipients, in terms of host guided-regeneration of new vessels, and we demonstrated that the AFSC secretome is responsible for the vascularising properties of these cells. We indentified in AFSC conditioned media (ACM) pro-angiogenic soluble factors, such as MCP-1, IL-8, SDF-1, VEGF. Our in vitro results suggest that ACM are cytoprotective, pro-differentiative and chemoattractive for endothelial cells. We also tested ACM on a pre-clinical model of hind-limb ischemic mouse, concluding that ACM contain mediators that promote the neo-arteriogenesis, as remodelling of pre-existing collateral arteries to conductance vessels, thus preventing the capillary loss and the tissue necrosis of distal muscles. In line with the current regenerative medicine trend, in the present study we assert the concept that stem cell-secreted mediators can guide the tissue repair by stimulating or recruiting host reparative cells.
大多数紧急的健康问题都与血管生成失败有关。使用来自不同来源或物种的干细胞进行体外和体内内皮工程，并不一定意味着它们直接朝着血管表型发展。在本研究中，我们使用人羊水干细胞（AFSC）在小鼠受体内引发强烈的血管生成反应，表现为宿主引导的新血管再生，我们证明了 AFSC 分泌组是这些细胞血管生成特性的原因。我们在 AFSC 条件培养基（ACM）中鉴定出了促血管生成的可溶性因子，如 MCP-1、IL-8、SDF-1 和 VEGF。我们的体外结果表明，ACM 对内皮细胞具有细胞保护、促分化和趋化作用。我们还在小鼠后肢缺血的临床前模型上测试了 ACM，得出结论 ACM 中含有促进新动脉生成的介质，即重塑预先存在的侧支动脉为传导血管，从而防止远端肌肉的毛细血管损失和组织坏死。与当前再生医学的趋势一致，在本研究中，我们主张干细胞分泌的介质可以通过刺激或招募宿主修复细胞来引导组织修复的概念。
