Artikel
Transplantation of long-term expanded human fetal neural precursor cells – evidence of distant migration and multi-lineage differentiation
Transplantation von langzeit-expandierten humanen fötalen neuronalen Vorläuferzellen: Indiz für ferne Migration und Differenzierung zu unterschiedlichen Zellpopulationen
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Veröffentlicht: | 8. Mai 2006 |
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Gliederung
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Objective: Cell replacement therapy based on human fetal cell transplantation proved to be beneficial under experimental conditions and in clinical trials. Ethical concerns and limited availability of the aborted tissue make it difficult to become a routine clinical strategy. The purpose of the present work was therefore prolonged in vitro expansion of human fetal-derived neural precursor cells and investigation of their behavior after intracerebral implantation.
Methods: Long-term expanded human fetal region-specific neural precursors were stereotactically grafted into intact rodent striata or hippocampi of adult immunosuppressed recipients. Graft survival, migration and the expression of the specific glial and neural markers by the implanted cells were investigated nine weeks post-grafting using standard immunohistochemical methods.
Results: All grafts survived up to nine weeks post-transplantation. Numerous intrastriatally implanted cells migrated to the adjacent parenchyma and entered white matter tracts to reach distant locations of the host brain such as the forceps minor and the surrounding cortex at the most frontal aspect of the CNS as well as the cerebral peduncle or the substantia nigra. Migrating cells were characterized by the expression of neuroepithelial stem cell marker nestin and often presented with a particular bi-polar morphology with a long body axis directed along the white matter fiber bundles. Some cells acquired a neuronal morphology with predominant GABAergic differentiation and the expression of marker typical for young migrating neuroblasts (doublecortin). However, most of the implanted cells remained undifferentiated, retaining the nestin expression and typical immature morphology. Intrahippocampal transplants were confined within the target structure and did not enter white matter tracts migrating preferentially towards the dentate gyrus and the hippocampal fissure. There was no difference in phenotypic differentiation between the hippocampal and the intrastriatal grafts.
Conclusions: Taken together, these data demonstrate good survival of the human neural xenografts in immunosuppressed animals, extensive migration of a nestin+ cells and relatively limited differentiation of the precursor cells towards more mature neuronal phenotypes such as GABA-producing neurons.