Angiogenic properties of human dental pulp stem cells.
Angiogenic properties of human dental pulp stem cells.
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DOI：
10.1371/journal.pone.0071104
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lambrichts I
中科院分区：
文献类型：
--
作者：
Bronckaers A;Hilkens P;Fanton Y;Struys T;Gervois P;Politis C;Martens W;Lambrichts I
血管生成，即从预先存在的血管形成毛细血管，是组织工程中的关键过程。如果不能迅速建立血液供应，则氧气和营养输送不足，植入组织将发生坏死。近年来的研究表明，人牙髓中含有具有自我更新和多向分化能力的前体细胞，称为牙髓干细胞（dental pulp stem cells，hDPSC）。由于这些细胞可以很容易地分离，培养和冷冻保存，它们代表了一个有吸引力的干细胞来源的组织工程。到目前为止，对hDPSC的血管生成能力和机制知之甚少。在这项研究中，通过抗体阵列测定hDPSC的细胞裂解物和条件培养基的血管生成谱。在mRNA和蛋白水平上发现了许多促血管生成和抗血管生成因子，如血管内皮生长因子（VEGF）、单核细胞趋化蛋白-1（MCP-1）、纤溶酶原激活物抑制剂-1（派-1）和内皮抑素（endostatin）。hDPSC对人微血管内皮细胞（HMEC-1）的增殖无影响，但能显著诱导HMEC-1迁移。向HMEC-1中添加PI 3 K抑制剂LY 294002和MEK抑制剂U 0126抑制了这种作用，表明Akt和ERK途径都参与了hDPSC介导的HMEC-1迁移。抗VEGF抗体也消除了hDPSC的趋化作用。此外，在鸡绒毛尿囊膜（CAM）测定中，hDPSC能够显著诱导血管形成。总之，hDPSC具有诱导血管生成的能力，这意味着该干细胞群体具有巨大的临床潜力，不仅用于组织工程，而且用于治疗慢性伤口、中风和心肌梗死。
Angiogenesis, the formation of capillaries from pre-existing blood vessels, is a key process in tissue engineering. If blood supply cannot be established rapidly, there is insufficient oxygen and nutrient transport and necrosis of the implanted tissue will occur. Recent studies indicate that the human dental pulp contains precursor cells, named dental pulp stem cells (hDPSC) that show self-renewal and multilineage differentiation capacity. Since these cells can be easily isolated, cultured and cryopreserved, they represent an attractive stem cell source for tissue engineering. Until now, only little is known about the angiogenic abilities and mechanisms of the hDPSC. In this study, the angiogenic profile of both cell lysates and conditioned medium of hDPSC was determined by means of an antibody array. Numerous pro-and anti-angiogenic factors such as vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1) and endostatin were found both at the mRNA and protein level. hDPSC had no influence on the proliferation of the human microvascular endothelial cells (HMEC-1), but were able to significantly induce HMEC-1 migration in vitro. Addition of the PI3K-inhibitor LY294002 and the MEK-inhibitor U0126 to the HMEC-1 inhibited this effect, suggesting that both Akt and ERK pathways are involved in hDPSC-mediated HMEC-1 migration. Antibodies against VEGF also abolished the chemotactic actions of hDPSC. Furthermore, in the chicken chorioallantoic membrane (CAM) assay, hDPSC were able to significantly induce blood vessel formation. In conclusion, hDPSC have the ability to induce angiogenesis, meaning that this stem cell population has a great clinical potential, not only for tissue engineering but also for the treatment of chronic wounds, stroke and myocardial infarctions.
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作者：
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