Magnetization transfer contrast MRI for non-invasive assessment of innate and adaptive immune responses against alginate-encapsulated cells

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.