磁性标记干细胞的无创磁共振成像直接识别胶质瘤模型中的新生血管。
Noninvasive MR imaging of magnetically labeled stem cells to directly identify neovasculature in a glioma model.
作者信息
Anderson Stasia A, Glod John, Arbab Ali S, Noel Martha, Ashari Parwana, Fine Howard A, Frank Joseph A
机构信息
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1074, USA.
出版信息
Blood. 2005 Jan 1;105(1):420-5. doi: 10.1182/blood-2004-06-2222. Epub 2004 Aug 26.
Bone marrow-derived endothelial precursor cells incorporate into neovasculature and have been successfully used as vehicles for gene delivery to brain tumors. To determine whether systemically administered Sca1+ bone marrow cells labeled with superparamagnetic iron oxide nanoparticles can be detected by in vivo magnetic resonance imaging in a mouse brain tumor model, mouse Sca1+ cells were labeled in vitro with ferumoxides-poly-L-lysine complexes. Labeled or control cells were administered intravenously to glioma-bearing severe combined immunodeficient (SCID) mice. Magnetic resonance imaging (MRI) was performed during tumor growth. Mice that received labeled cells demonstrated hypointense regions within the tumor that evolved over time and developed a continuous dark hypointense ring at a consistent time point. This effect was not cleared by administration of a gadolinium contrast agent. Histology showed iron-labeled cells around the tumor rim in labeled mice, which expressed CD31 and von Willebrand factor, indicating the transplanted cells detected in the tumor have differentiated into endothelial-like cells. These results demonstrate that MRI can detect the incorporation of magnetically labeled bone marrow-derived precursor cells into tumor vasculature as part of ongoing angiogenesis and neovascularization. This technique can be used to directly identify neovasculature in vivo and to facilitate gene therapy by noninvasively monitoring these cells as gene delivery vectors.
骨髓来源的内皮前体细胞可整合到新生血管中,并已成功用作向脑肿瘤进行基因递送的载体。为了确定在小鼠脑肿瘤模型中,通过体内磁共振成像是否能够检测到经超顺磁性氧化铁纳米颗粒标记的全身给药的Sca1⁺骨髓细胞,将小鼠Sca1⁺细胞在体外与菲立磁-聚-L-赖氨酸复合物进行标记。将标记的细胞或对照细胞静脉注射给荷胶质瘤的严重联合免疫缺陷(SCID)小鼠。在肿瘤生长过程中进行磁共振成像(MRI)。接受标记细胞的小鼠在肿瘤内显示出随时间演变的低信号区域,并在一个一致的时间点形成连续的暗低信号环。给予钆对比剂并未消除这种效应。组织学显示,标记小鼠肿瘤边缘周围有铁标记的细胞,这些细胞表达CD31和血管性血友病因子,表明在肿瘤中检测到的移植细胞已分化为内皮样细胞。这些结果表明,MRI能够检测到磁性标记的骨髓来源前体细胞整合到肿瘤血管系统中,作为正在进行的血管生成和新生血管形成的一部分。该技术可用于在体内直接识别新生血管,并通过将这些细胞作为基因递送载体进行无创监测来促进基因治疗。