22-07-08(16:45:53)
Authors:
J. Maciaczyk, U. Kahlert, , D. Maciaczyk, G. Nikkhah
Institutions:
Laboratory Molecular Neurosurgery, Department of Stereotactic and Functional Neurosurgery, Neurocentre, University of Freiburg, Breisacher Str. 64, 79106 Freiburg i. B., Germany
Title of abstract : Long-distance migration and multi-lineage differentiation of fetal human neural stem cells after transplantation into the rat brain
Abstract text:
Transplantation of human fetal neural tissue clearly shows beneficial effects in animal models and clinical trials of human diseases. Therefore, neuororeplacement therapy might become a valuable therapeutical alternative for patients with neurordegenerative diseases as well as after CNS injury or stroke. The limited availability of human neural stem cells (hNSCs) derived from fetal neuraxis prompted us to expand these cells in vitro for an extended period of time and to study their potential after intracerebral implantation. hNSCs derived from different fetal brain regions (neocortex, striatum, midbrain, spinal cord) were grafted into the rodent striatum and hippocampus after culturing. All grafts survived up to 9 weeks post-transplantation. In general, hNSCs derived from neocortex and striatum generated larger grafts and showed more widespread cell migration as compared to hNSCs from midbrain and spinal cord. In addition, cells that were grafted into the striatum migrated more distant compared to those implanted in the hippocampus. Typically, a number of hNSCs transplanted into the striatum were found to extensively migrate along the white matter tracts reaching both rostral (anterior corpus callosum with overlying cortex) and caudal (midbrain) brain regions. Consistently, the vast majority of migratory cells expressed the stem cell marker nestin even after 9 weeks. However, a fraction of grafted cells acquired a neuronal morphology and expressed doublecortin, βIII tubulin or GABA. Taken together, these data demonstrate long-term survival, long-distance migration, and neuronal differentiation of in vitro expanded hNSCs after transplantation. The fact of a large pool of grafted nestin-positive cells offers the possibility of further in vivo manipulation and recruitment of different neural phenotypes for cell replacement strategies in the CNS.
