The high integration and differentiation potential of autologous neural stem cell transplantation compared with allogeneic transplantation in adult rat hippocampus

Abstract

Cell therapy is thought to have a central role in restorative therapy, which aims to restore function to the damaged nervous system. The purpose of this study was to establish an autologous neural stem cell (NSC) transplantation model using adult rats and to compare survival, migration, and differentiation between this system and allogeneic NSC transplantation. Furthermore, we compared the immunologic response of the host tissue between autologous and allogeneic transplantation. NSCs were removed from the subventricular zone of adult Fischer 344 rats using stereotactic methods. NSCs were expanded and microinjected into normal hippocampus in the autologous brain. Allogeneic NSC (derived from adult Wistar rats) transplantation was performed using the same procedure, and hippocampal sections were analyzed immunohistologically 3 weeks post-transplantation. The cell survival and migration rate were higher for autologous transplantation than for allogeneic transplantation, and the neuronal differentiation rate in the autologous transplanted cells far exceeded that of allogeneic transplantation. Furthermore, there was less astrocyte and microglia reactivity in the host tissue of the autologous transplantation compared with allogeneic transplantation. These findings demonstrate that immunoreactivity of the host tissue strongly influences cell transplantation in the CNS as the autologous transplantation did not induce host tissue immunoreactivity; the microenvironment was essentially maintained in an optimal condition for the transplanted cells.

Generation of Functional Dopamine Neurons from Neural Precursor Cells Isolated from the Subventricular Zone and White Matter of the Adult Rat Brain Using Nurr1 Overexpression

“…Consistent with preferred in vitro astroglial differentiation potentials of adult brain-derived neurospheres [37][38][39], 40%-50% of the SVZ and WM NP cells differentiated into GFAPϩ astrocytes. The preferential astrocytic differentiation of WMderived NP cells in this study is in contrast to the finding of Nunes et al [10] that most WM NP cells derived from purified oligodendrocyte progenitors retained differentiation toward oligodendrocytic progeny.…”

Bax siRNA promotes survival of cultured and allografted granule cell precursors through blockade of caspase-3 cleavage

“…33 However, the majority of grafted precursors are subjected to death during the first hours following their transplantation. 16 The death pathways activated upon allografting have not yet been completely understood.…”

Prospects for Neural Stem Cell-Based Therapies for Neurological Diseases

“…8 In addition immunogenicity of NSC is pertinent for survival, because allogeneic neural stem cells can not survive in the host without immunosupression. 134 Both embryonic and adult neural progenitor cells may express major histocompatibility complex class I and co-stimulatory molecules, but they do not express surface class II molecules, and thus they are considered less immunogenic than differentiated cells. However, during inflammation, molecules that render NSCs immunogenic are upregulated.…”