The use of magnetic resonance imaging to follow glial cells transplanted into the central nervous system

The aim of this thesis was to evaluate the use of magnetic resonance (MR) imaging to trace glial cells with therapeutic potential following transplantation into the demyelinated rodent CNS. The in vitro labelling potential of the peripheral (PNS) and central nervous system (CNS) glial cells with two MR contrast agents, superparamagnetic-iron oxide (SPIO) and magnetic microspheres (MMs) was determined. Transplants of labelled cells were then evaluated for retention of function in vivo. Following transplantation into the lesioned rodent CNS, both SPIO and MMs enabled labelled cells to be followed in vivo for up to 4 weeks post-transplantation using T2-weighted MR imaging. Serial MRI studies showed that it was possible to follow transplants within the same animal repeatedly and that the in vivo and ex vivo images correlated with both the persistence of SPIO-labelled cells and also remyelination. The fate of transplanted SPIO-labelled SCs was followed for up to 7 months using MRI. An important caveat identified was the potential for endogenous blood breakdown products to produce a similar, though less intense, signal on MRI. However, this signal was suppressible using magnetisation transfer imaging sequences. Histological assessment of the transplant sites in animals receiving labelled cells showed widespread remyelination similar to that in controls. Using electron microscopy, cells containing SPIO inclusions and MMs were seen elaborating peripheral-type myelin sheaths. Both types of contrast agent could also be seen within host-derived phagocytic cells using electron microscopy. However, myelinating cells, containing MMs, contributed most significantly to the overall signal reduction. These results provide important data demonstrating the use of MRI to follow the fates of glial cells transplanted into the rodent CNS having been pre-labelled in vitro with MR contrast agents for up to 7 months.EThOS - Electronic Theses Online ServiceGBUnited Kingdo