この研究は、著者の仮説である「ELF-EMFによる抗血管新生作用」のメカニズムを調査するために、内皮細胞モデルに50 Hz、2 mTの正弦波磁界（MF）ばく露を与え、その細胞の状態、増殖、運動性、細管形成能力を測定した。内皮細胞モデルには、ヒト臍帯静脈血管内皮細胞HUVECおよびマウス膵臓由来内皮細胞株MS-1を用いた。その結果、マウスに移植されたMS-1細胞は急速な腫瘍様増殖を明らかに示すが、MFばく露を与えたMS-1細胞を移植されたマウスにおいてはそのような増殖は有意に低下した；MFばく露MS-1細胞を移植されたマウス由来の腫瘍の組織学的分析では、血管腫のサイズ、血液充満空間、および出血の減少が示された；MFばく露MS-1細胞のインビトロでの増殖も有意に抑制された；また、MFばく露は、HUVECにおける増殖、遊走、および細管様構造形成のプロセスを低下させることも示された；また、MFばく露は、血管内皮増殖因子（VEGF2）の発現と活性化レベルを有意に低下させることが示され、細胞膜に配置されたVEGF受容体に対するMFの直接的または間接的な影響が示唆された、と報告している。
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To evaluate the angiogenesis in two endothelial cell models exposed to an extremely low frequency magnetic field in vivo and in vitro.
The inhibition of angiogenesis could represent a possible therapeutic strategy in diseases where an excessive angiogenesis is involved (for example cancer).
For the in vivo experiments, exposed (72 hours) or not exposed mouse endothelial cells (MS-1, tumor promoting) cells were injected subcutaneously into the flanks of mice and tumor development was observed for 7 days. For the in vitro experiments, MS-1 cells and human umbilical endothelial cells (HUVECs) cells were exposed for up to 24 and 72 hours, respectively.
Vascular endothelial growth factor (VEGF) is a signal protein that (amongst others) stimulates angiogenesis.
|continuous for up to 24 h
|Helmholtz coils were placed in an incubator at 37°C, 5 % CO2, 95 % air and 100 % relative humidity
|Helmholtz coils had a mean radius of 13 cm, in each coil the number of turns was 800 with a 2 mm² wire giving a resulting resistance of 2.4 Ohm and an inductance of ca. 39 mH, mean vertical distance between the coils was 13.5 cm; simultaneous exposure of a maximum of 6 culture plates
|A sham exposure was conducted.
|continuous for 72 hours
|A sham exposure was conducted.
Mice inoculated with magnetic field exposed MS-1 cells developed significant smaller tumors than mice inoculated with sham exposed MS-1 cells. The histopathological examination of the tumors indicated a reduction of hemangioma (a benign tumor) size, of blood-filled spaces, and in hemorrhage in mice with exposed cells compared to mice with sham exposed MS-1 cells. Also in vitro analysis of MS-1 cells showed that the magnetic field exposure significantly decreased cell proliferation.
In exposed human umbilical vein endothelial cells, cell proliferation, migration and formation of tubule-like formation was significantly dereased compared to sham exposed cells. Additionally, the protein expression level of vascular endothelial growth factor and phosphorylated vascular endothelial growth factor was significantly down-regulated in exposed human umbilical vein endothelial cells compared to sham exposed ones.
The authors conclude that the magnetic field exposure reduced the ability of endothelial cells to form new vessels in vivo and in vitro, probably via an vascular endothelial growth factor pathway. These findings could help to develop therapeutic applications for the treatment of diseases with involved angiogenesis.