Animal model of human medulloblastoma: clinical, magnetic resonance imaging, and histopathological findings after intra-cisternal injection of MHH-MED-1 cells into nude rats.

Abstract

To establish an animal model of human medulloblastoma, we have injected human MHH-MED-1 cells into the cisterna magna of nude rats. Tumors grew in 3 out of 4 animals injected with 10(6) medulloblastoma cells. Affected animals showed little or no weight gain and eventually lost weight but did not develop obvious neurological symptoms until the end of observation on day 31 after inoculation. At this time, magnetic resonance imaging (MRI) in tumor-bearing rats revealed contrast enhancement in the region of the fourth ventricle and the cisterna magna. Neuropathological examination demonstrated corresponding leptomeningeal growth in the cisterna magna invading the medulla oblongata, and tumor growth within the fourth ventricle invading the pons. The tumors basically showed the same immunostaining pattern as MHH-MED-1 cells in vitro expressing neuron-specific enolase (NSE) and vimentin, but no neurofilaments (NFs), synapthophysin, or glial fibrillary acidic protein (GFAP). No tumor grew in the fourth animal, which had a normal weight gain and no alteration on MRI. In conclusion (1) the intrathecally injected human medulloblastoma cells spread similar to medulloblastomas in patients, (2) tumor growth is readily detected by MRI, (3) the new animal model is a suitable tool for further experimental research including intrathecal therapeutic studies.

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