Chan Kannie W Y, Liu Guanshu, van Zijl Peter C M, Bulte Jeff W M, McMahon Michael T
Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205, USA; Center of Nanomedicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, Baltimore, MD 21205, USA.
Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205, USA.
Biomaterials. 2014 Sep;35(27):7811-8. doi: 10.1016/j.biomaterials.2014.05.057. Epub 2014 Jun 13.
By means of physical isolation of cells inside semi-permeable hydrogels, encapsulation has been widely used to immunoprotect transplanted cells. While spherical alginate microcapsules are now being used clinically, there still is little known about the patient's immune system response unless biopsies are obtained. We investigated the use of Magnetization Transfer (MT) imaging to non-invasively detect host immune responses against alginate capsules containing xenografted human hepatocytes in four groups of animals, including transplanted empty capsules (-Cells/-IS), capsules with live cells with (+LiveCells/+IS) and without immunosuppression (+LiveCells/-IS), and capsules with apoptotic cells in non-immunosuppressed animals (+DeadCells/-IS). The highest MT ratio (MTR) was found in +LiveCells/-IS, which increased from day 0 by 38% and 53% on days 7 and 14 after transplantation respectively, and corresponded to a distinctive increase in cell infiltration on histology. Furthermore, we show that macromolecular ratio maps based on MT data are more sensitive to cell infiltration and fibrosis than conventional MTR maps. Such maps showed a significant difference between +LiveCells/-IS (0.18 ± 0.02) and +DeadCells/-IS (0.13 ± 0.02) on day 7 (P < 0.01) existed, which was not observed on MTR imaging. We conclude that MT imaging, which is clinically available, can be applied for non-invasive monitoring of the occurrence of a host immune response against encapsulated cells.
通过将细胞物理隔离在半透性水凝胶内部，包封已被广泛用于对移植细胞进行免疫保护。虽然球形藻酸盐微胶囊目前正在临床中使用，但除非进行活检，否则对患者免疫系统反应仍知之甚少。我们研究了利用磁化传递（MT）成像技术，对四组动物体内针对含有异种移植人肝细胞的藻酸盐胶囊的宿主免疫反应进行无创检测，这四组包括移植空胶囊（-细胞/-免疫抑制）、有活细胞的胶囊（+活细胞/+免疫抑制）和无免疫抑制的情况（+活细胞/-免疫抑制），以及在未免疫抑制动物体内含有凋亡细胞的胶囊（+死亡细胞/-免疫抑制）。在+活细胞/-免疫抑制组中发现了最高的MT比率（MTR），其在移植后第0天开始增加，在第7天和第14天分别增加了38%和53%，并且在组织学上对应着细胞浸润的显著增加。此外，我们表明基于MT数据的大分子比率图比传统的MTR图对细胞浸润和纤维化更敏感。这样的图显示在第7天+活细胞/-免疫抑制组（0.18±0.02）和+死亡细胞/-免疫抑制组（0.13±0.02）之间存在显著差异（P<0.01），而在MTR成像中未观察到这种差异。我们得出结论，临床可用的MT成像可用于对针对包封细胞的宿主免疫反应的发生进行无创监测。
