Parshyna Iryna, Lehmann Susann, Grahl Katrin, Pahlke Claudia, Frenzel Annika, Weidlich Helmut, Morawietz Henning
Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital and Medical Faculty Carl Gustav Carus, TU Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
Institute Prof. Dr. Georg Kurz GmbH, Cologne, Germany.
Atheroscler Suppl. 2017 Nov;30:303-310. doi: 10.1016/j.atherosclerosissup.2017.05.040.
Human adipose-tissue derived stem cells (ADSC) are interesting novel targets in tissue engineering and regenerative medicine with pronounced angiogenic capacities. Furthermore, omega-3 fatty acids have been described to mediate cardioprotective effects, but their role in angiogenesis and vascular regeneration is not well-understood. Here, we analyzed the impact of different omega-3 fatty acids on angiogenesis by ADSCs.
Stem cells were cultured as monolayers or in 3D models, in spheroids embedded in collagen matrix or in co-cultures with human umbilical vein endothelial cells (HUVECs) in the Matrigel™ assay. The angiogenic properties of ADSCs were assessed by their sprouting and paracrine activities, gene expression by RT-PCR, Western blot, and enzyme immunoassay.
Stimulation of undifferentiated ADSCs with docosahexaenoic acid (DHA) strongly upregulated angiopoietin-1 mRNA levels up to 4.6 ± 0.3 fold. Furthermore, Il-6 and Il-8 mRNAs were increased 4.2 ± 0.5 fold and 7.1 ± 1.1 fold, respectively. On the other hand, addition of DHA significantly decreased the cumulative sprout length by 2.7 ± 0.8 fold and reduced the total number of sprouts by 2.3 ± 0.9 fold in the in vitro angiogenesis assay. Moreover, excretion of IL-8 into the medium rapidly increased up to 1.7 ± 0.3 fold in response to treatment of ADSCs with DHA. Finally, protein kinase C inhibitor RO-31-8220 abrogated DHA-mediated up-regulation of angiopoietin-1 without significantly affecting ADSCs cell viability.
In conclusion, ADSCs might regulate the formation and function of microvascular networks.
人脂肪组织来源的干细胞（ADSC）是组织工程和再生医学中具有显著血管生成能力的新型有趣靶点。此外，ω-3脂肪酸已被描述具有心脏保护作用，但其在血管生成和血管再生中的作用尚不清楚。在此，我们分析了不同ω-3脂肪酸对ADSC血管生成的影响。
干细胞以单层或三维模型培养，在胶原基质包埋的球体中培养，或在基质胶检测中与人脐静脉内皮细胞（HUVEC）共培养。通过其发芽和旁分泌活性、逆转录-聚合酶链反应（RT-PCR）、蛋白质印迹法和酶免疫测定法评估ADSC的血管生成特性。
用二十二碳六烯酸（DHA）刺激未分化的ADSC可使血管生成素-1 mRNA水平强烈上调至4.6±0.3倍。此外，白细胞介素-6（Il-6）和白细胞介素-8（Il-8）mRNA分别增加4.2±0.5倍和7.1±1.1倍。另一方面，在体外血管生成试验中，添加DHA可使累积芽长度显著降低2.7±0.8倍，并使芽总数减少2.3±0.9倍。此外，用DHA处理ADSC后，IL-8向培养基中的分泌迅速增加至1.7±0.3倍。最后，蛋白激酶C抑制剂RO-31-8220消除了DHA介导的血管生成素-1上调，而对ADSC细胞活力无显著影响。
总之，ADSC可能调节微血管网络的形成和功能。
