gms | German Medical Science

57th Annual Meeting of the German Society of Neurosurgery
Joint Meeting with the Japanese Neurosurgical Society

German Society of Neurosurgery (DGNC)

11 - 14 May, Essen

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

Meeting Abstract

  • J. Maciaczyk - Abteilung für Stereotaktische und Funktionelle Neurochirurgie, Neurozentrum, Universitätsklinikum Freiburg
  • corresponding author D. Maciaczyk - Abteilung für Stereotaktische und Funktionelle Neurochirurgie, Neurozentrum, Universitätsklinikum Freiburg
  • A. Klein - Abteilung für Stereotaktische und Funktionelle Neurochirurgie, Neurozentrum, Universitätsklinikum Freiburg
  • G. Nikkhah - Abteilung für Stereotaktische und Funktionelle Neurochirurgie, Neurozentrum, Universitätsklinikum Freiburg

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 57. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. Essen, 11.-14.05.2006. Düsseldorf, Köln: German Medical Science; 2006. DocP 06.92

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2006/06dgnc309.shtml

Published: May 8, 2006

© 2006 Maciaczyk et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

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.