Abstract
Adult bone marrow stroma contains multipotent stem cells (BMSC) that are a mixed population of mesenchymal and neural-crest derived stem cells. Both cells are endowed with in vitro multi-lineage differentiation abilities, then constituting an attractive and easy-available source of material for cell therapy in neurological disorders. Whereas the in vivo integration and differentiation of BMSC in neurons into the central nervous system is currently matter of debate, we report here that once injected into the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, pure populations of either bone marrow neural crest stem cells (NCSC) or mesenchymal stem cells (MSC) survived only transiently into the lesioned brain. Moreover, they do not migrate through the brain tissue, neither modify their initial phenotype, while no recovery of the dopaminergic system integrity was observed. Consequently, we tend to conclude that MSC/NCSC are not able to replace lost neurons in acute MPTP-lesioned dopaminergic system through a suitable integration and/or differentiation process. Altogether with recent data, it appears that neuroprotective, neurotrophic and anti-inflammatory features characterizing BMSC are of greater interest as regards CNS lesions management.
Highlights
The treatment of neurological disorders represents a critical issue in clinical research, since no complete functional recovery can be achieved with current therapeutic means, despite symptomatic improvements
Marrow Since we previously demonstrated that neural crest stem cells were mainly composed of nestin-positive cells [22 retracted in 55] and that the number of nestin-positive cells increased with the number of passages [25 retracted in 56], we decided to perform clonal selection of NCSC and mesenchymal stem cells (MSC) starting from passage 5, which should theoretically give us equal chances to isolate NCSC or MSC
To the light of those observations, the main objective of this study was to determine if bone marrow neural crest stem cells (NCSC) were responsible for the positive impact of bone marrow stromal cells in several PD models rather than mesenchymal stem cells (MSC)
Summary
The treatment of neurological disorders represents a critical issue in clinical research, since no complete functional recovery can be achieved with current therapeutic means, despite symptomatic improvements. While neurons have already been successfully generated from embryonic stem cells (ES) [4,5] or induced pluripotent stem cells (iPS) [6,7], the use of adult somatic stem cells definitely remains of significant interest regarding technical, ethical and immunological issues concerning cell transplantation for brain-related diseases. In this regard, bone marrow stromal cells (BMSC) represent an important source of -accessible multipotent cells to use in a cell therapy purpose [8]
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