Davis John P, Salmon Morgan, Pope Nicolas H, Lu Guanyi, Su Gang, Sharma Ashish K, Ailawadi Gorav, Upchurch Gilbert R
Division of Vascular and Endovascular Surgery and Cardiothoracic Surgery, Department of Surgery, University of Virginia School of Medicine, Charlottesville, Virginia.
Division of Vascular and Endovascular Surgery and Cardiothoracic Surgery, Department of Surgery, University of Virginia School of Medicine, Charlottesville, Virginia.
J Surg Res. 2015 Nov;199(1):249-58. doi: 10.1016/j.jss.2015.04.025. Epub 2015 Apr 14.
No medical therapies are yet available to slow abdominal aortic aneurysm (AAA) growth. This study sought to investigate the effect of different genders of bone marrow-derived mesenchymal stem cells (MSC) on AAA growth in a murine AAA model. Given the decreased rate of AAA in women, it is hypothesized that female MSC would attenuate AAA growth more so than male MSC.
Aortas of 8-10-wk-old male C57Bl/6 mice were perfused with purified porcine pancreatic elastase to induce AAA formation. Bone marrow-derived MSC from male and female mice were dosed via tail vein injection (3 million cells per dose, 500 μL of volume per injection) on postaortic perfusion days 1, 3, and 5. Aortas were harvested after 14 d.
Mean aortic dilation in the elastase group was 121 ± 5.2% (mean ± standard error of the mean), while male MSC inhibited AAA growth (87.8 ± 6.9%, P = 0.008) compared with that of elastase. Female MSC showed the most marked attenuation of AAA growth (75.2 ± 8.3% P = 0.0004). Proinflammatory cytokines tumor necrosis factor α, interleukin 1β, and monocyte chemotactic protein-1 (MCP-1) were only decreased in tissues treated with female MSC (P = 0.017, P = 0.001, and P < 0.0001, respectively, when compared with elastase).
These data exhibit that female MSC more strongly attenuate AAA growth in the murine model. Furthermore, female MSC and male MSC inhibit proinflammatory cytokines at varying levels. The effects of MSC on aortic tissue offer a promising insight into biologic therapies for future medical treatment of AAAs in humans.
目前尚无医学疗法可减缓腹主动脉瘤(AAA)的生长。本研究旨在探讨不同性别的骨髓间充质干细胞(MSC)对小鼠AAA模型中AAA生长的影响。鉴于女性AAA发病率较低,推测雌性MSC比雄性MSC更能减轻AAA的生长。
用纯化的猪胰弹性蛋白酶灌注8 - 10周龄雄性C57Bl/6小鼠的主动脉以诱导AAA形成。在主动脉灌注后的第1、3和5天,通过尾静脉注射给予来自雄性和雌性小鼠的骨髓间充质干细胞(每剂量300万个细胞,每次注射体积500μL)。14天后收获主动脉。
弹性蛋白酶组的平均主动脉扩张为121±5.2%(平均值±平均标准误差),而与弹性蛋白酶组相比,雄性MSC抑制了AAA的生长(87.8±6.9%,P = 0.008)。雌性MSC对AAA生长的抑制最为显著(75.2±8.3%,P = 0.0004)。促炎细胞因子肿瘤坏死因子α、白细胞介素1β和单核细胞趋化蛋白 - 1(MCP - 1)仅在接受雌性MSC治疗的组织中减少(与弹性蛋白酶组相比,P分别为0.017、0.001和P < 0.0001)。
这些数据表明,在小鼠模型中雌性MSC更能有效减轻AAA的生长。此外,雌性MSC和雄性MSC对促炎细胞因子的抑制水平不同。MSC对主动脉组织的作用为人类AAA未来的生物治疗提供了有前景的见解。