Shen Zhenglei, Gu Xuezhong, Mao Wenwen, Cao Honghua, Zhang Rui, Zhou Yeying, Liu Kunmei, Wang Lilan, Zhang Zhe, Yin Liefen
Department of Hematology, The Third Affiliated Hospital of Kunming Medical University Kunming, China.
Department of Hematology, The First People Hospital in Yunnan Province Kunming, China.
Am J Transl Res. 2019 May 15;11(5):2816-2829. eCollection 2019.
This study aimed to explore role of dendritic cells (DCs) fused with endothelial progenitor cells (EPCs) in inhibiting angiogenesis in acute myeloid leukemia (AML) mice. EPCs were isolated from human AML bone marrow mononuclear cells and fused with DCs, which were then injected back into AML mice. Changes in leukemia cells, micro-vessel density (MVD), early EPC molecular markers vascular endothelial growth factor receptor 2 (VEGFR2/KDR) and CD133 in bone marrow were measured. The results indicated that CD133 and KDR expression in EPCs was significantly higher than in epithelial cells (HUVECs). There were 46.14% ± 8.21% DCs doubly positive for VEGFR2 and CD11c, and it was 8.53% ± 1.27% in co-culture group. Fusion rate of DC/EPCs was 37.61% ± 6.94%, and 35.63% ± 6.09% in DC/ECs group. Growth rate of DC/EPCs was faster than that of EPCs (<0.05). At 14-20 days after fused cells injection, symptoms gradually decreased. There were a greater number of micro-vessels in bone marrow biopsy sections of AML mice than in normal controls (<0.05). There was slightly lower MVD in EC/DCs compared with EPC/DCs (>0.05). Positive expression of CD133 and VEGFR2 in bone marrow biopsies of AML mice was significantly higher than that in control mice (<0.05). Positive expression of CD133 and VEGFR2 in DC/EC fused cells was significantly lower than that before fusion (<0.05). In conclusion, DC-EPCs play a certain immunosuppressive effect on angiogenesis in AML mice. Our findings provide experimental data support for the construction of a cell vaccine with anti-angiogenic effect.
本研究旨在探讨树突状细胞(DCs)与内皮祖细胞(EPCs)融合在抑制急性髓系白血病(AML)小鼠血管生成中的作用。从人AML骨髓单个核细胞中分离出EPCs,并与DCs融合,然后将其回注到AML小鼠体内。检测白血病细胞、微血管密度(MVD)、骨髓中早期EPC分子标志物血管内皮生长因子受体2(VEGFR2/KDR)和CD133的变化。结果表明,EPCs中CD133和KDR的表达明显高于上皮细胞(人脐静脉内皮细胞,HUVECs)。VEGFR2和CD11c双阳性的DCs占46.14%±8.21%,共培养组为8.53%±1.27%。DC/EPCs的融合率为37.61%±6.94%,DC/ECs组为35.63%±6.09%。DC/EPCs的生长速度比EPCs快(P<0.05)。注射融合细胞后14 - 20天,症状逐渐减轻。AML小鼠骨髓活检切片中的微血管数量比正常对照组多(P<0.05)。与EPC/DCs相比,EC/DCs的MVD略低(P>0.05)。AML小鼠骨髓活检中CD133和VEGFR2的阳性表达明显高于对照小鼠(P<0.05)。DC/EC融合细胞中CD133和VEGFR2的阳性表达明显低于融合前(P<0.05)。总之,DC - EPCs对AML小鼠的血管生成具有一定的免疫抑制作用。我们的研究结果为构建具有抗血管生成作用的细胞疫苗提供了实验数据支持。