In-Vivo Imaging Of Transplanted Human Hepatic Stem Cells: Negative Contrast Labeling And 7t Micro-MRI Tracking

摘要

Stem cell therapies have great potential as alternative options to whole organ transplantations in treating dysfunction or failure, and alleviating the chronic shortage of donor availability of organs such as the liver. In these therapies, adherent stem cells are transplanted to replace and repopulate diseased tissues, hence allowing the failing organs to regain their functional effectiveness. Given that clinical trials are ongoing or are about to occur with many different categories of stem cells, there is a need for in vivo stem cell imaging to monitor cell motility after inoculation, and to follow the location and expansion of the stem cells thereafter. Specifically, some topics being addressed comprise cell transplantation procedures, cell migration dynamics, and possibilities for creating tissue-cell-vacuums to permit engraftment and expansion of the transplanted cells. In this way, the efficacy of stem cell therapy may be evaluated and realized. The goals of the current study are to develop effective procedures for labeling stem cells with contrast agents for magnetic resonance imaging (MRI), and to investigate the MRI detectability of labeled cells. The model systems are human hepatic stem cells that are isolated by fractionation or immunoselection technologies from human fetal livers. In brief, there are two subpopulations of human hepatic stem cells, both of which are positive for Epithelial Cell Adhesion molecule (EpCAM) as well as for other antigens (Moss, Wauthier et al. 2004). The uptake, retention and physiological effects of magnetic labels are examined with in vitro experiments. Subsequently, the human hepatic stem cells are transplanted into immunocompromised SCID/nod mice to monitor in vivo MRI cell signals. To facilitate time-lapse investigations, several animals are inoculated simultaneously but independently imaged in order to quantify signal intensities, durations, and spatial distributions of cells within resident mice livers.