Intracerebroventricular administration of human umbilical cord blood cells delays disease progression in two murine models of motor neuron degeneration.

Abstract

The lack of effective drug therapies for motor neuron diseases (MND), and in general for all the neurodegenerative disorders, has increased the interest toward the potential use of stem cells. Among the cell therapy approaches so far tested in MND animal models, systemic injection of human cord blood mononuclear cells (HuCB-MNCs) has proven to reproducibly increase, although modestly, the life span of SOD1G93A mice, a model of familial amyotrophic lateral sclerosis (ALS), even if only few transplanted cells were found in the damaged areas. In attempt to improve the potential efficacy of these cells in the central nervous system, we examined the effect and distribution of Hoechst 33258-labeled HuCB-MNCs after a single bilateral intracerberoventricular injection in two models of motor neuron degeneration, the transgenic SOD1G93A and wobbler mice. HuCB-MNCs significantly ameliorated symptoms progression in both mouse models and prolonged survival in SOD1G93A mice. They were localized in the lateral ventricles, even 4 months after administration. However, HuCB-MNCs were not found in the spinal cord ventral horns. This evidence strengthens the hypothesis that the beneficial role of transplanted cells is not due to cell replacement but is rather associated with the production and release of circulating protective factors that may act both at the central and/or peripheral levels. In particular, we show that HuCB-MNCs release a series of cytokines and chemokines with antiinflammatory properties that could be responsible of the functional improvement of mouse models of motor neuron degenerative disorders.

DOI: 10.1089/rej.2011.1197

Cite this paper

@article{Bigini2011IntracerebroventricularAO, title={Intracerebroventricular administration of human umbilical cord blood cells delays disease progression in two murine models of motor neuron degeneration.}, author={Paolo Bigini and Pietro Veglianese and Gabriella Andriolo and Lidia Cova and Giuliano Grignaschi and Ilaria Caron and Cristina Daleno and Sara Barbera and Arianna Ottolina and Cinzia Calzarossa and Lorenza Lazzari and Tiziana Mennini and Caterina Bendotti and Vincenzo Silani}, journal={Rejuvenation research}, year={2011}, volume={14 6}, pages={623-39} }