Stem cell factor and mesenchymal and neural stem cell transplantation in a rat model of Huntington's disease

Abstract

Neural and mesenchymal stem cells have been proposed as alternative sources of cells for transplantation into the brain in neurodegenerative disorders. However, the endogenous factors controlling their engraftment within the injured parenchyma remain ill-defined. Here, we demonstrate significant engraftment of undifferentiated exogenous mesenchymal or neural stem cells throughout the lesioned area in a rat model for Huntington's disease, as late as 8 weeks post-transplantation. We show that stem cell factor (SCF), strongly up-regulated within host cells in the damaged striatum, is able to activate the SCF receptor c-kit and its signaling pathway and to promote the migration and proliferation of mesenchymal and neural stem cells in vitro. Furthermore, c-kit receptor blockade alters neural stem cell distribution within the lesioned striatum. Host SCF expression is observed in atypical cells expressing glial fibrillary acidic protein and doublecortin in the lesioned striatum and in migrating doublecortin-positive progenitors. Taken together, these data demonstrate that SCF produced in situ in the lesioned striatum is an important factor in promoting the engraftment of stem cells within the lesioned brain.

Grafting Neural Precursor Cells Promotes Functional Recovery in an SCA1 Mouse Model

“…Dysfunctional or morphologically altered PCs, but in normal or nearly normal number, did not generate a strong enough signal to attract NPCs. The nature of the attractive signal is not determined, but we know that in other systems (basal ganglia, brain hemispheres), growth factors (Ghosh and Greenberg, 1995;Kuhn et al, 1997;Zhang et al, 2003) and chemokines (Imitola et al, 2004;Bantubungi et al, 2008) (S. Chintawar, A. Ravella, M. Pandolfo unpublished results) generated at the site of injury can act as a migratory and/or a prodifferentiating factor. Grafted NPCs that remained near the injection sites in the white matter generally adopted an astroglial phenotype and were GFAP pos .…”

Advances in the Combined Use of Adult Cell Therapy and Scaffolds for Brain Tissue Engineering

“…Thus, it was suggested that MSCs, by producing growth factors, allowed surviving cells within the caudate nucleus to function more efficiently and to facilitate other compensatory responses (Dunbar et al, 2006). In this regard, another study demonstrated the importance of factors such as stem cell factor (SCF), produced in situ in the lesioned striatum, to promote the migration and engraftment of MSCs via SCF receptor c-kit (Bantubungi et al, 2008). In the context of PD, several teams, including ours, reported the neuronal differentiation of human MSCs toward a dopaminergic phenotype in vitro, indicating that these cells may constitute an alternative dopamine secreting source of cells (Trzaska & Rameshwar, 2011;Barzilay et al, 2008;Trzaska et al, 2007;).…”

A Surgical Technique for Homogenous Renal Distribution of Substances in Rats

“…In theory, this injection should be performed as close as possible to the target organ. In the past, intrarenal injection was considered the optimal route for cell transplantation to the kidney since it is the closest to the target organ [11]. However, cells transplanted by this route usually failed to ameliorate the disease pathology in the kidney as the limited diffusion of nutrients and oxygen [12] was insufficient for successful engraftment of the cells.…”

“…In this case, the cells are preferentially administered into the aorta [3,10] or even the carotid artery [11], as the first pass through the lungs prevents many cells from reaching the kidney immediately after the injection. Nevertheless, as stem cells are known to home to sites of inflammation [13], a systemic injection remains a defendable strategy.…”