Abstract :
[en] Parkinson’s disease (PD) is the second most common neurodegenerative disorder in industrialized countries. Its main characteristic relies in a progressive loss of dopaminergic (DA) neurons in the Substantia Nigra pars compacta (SNpc), resulting in a deficient dopamine release in the striatum and then promoting important defects in motility regulation. Unfortunately, motor symptoms are generally diagnosed once 80% of nigrostriatal neurons are already lost. The emergence of neuroprotective/-restorative strategies is then increasingly raising hope, and a lot of people now focus on cell therapy experiments. Adult bone marrow stromal stem cells (BMSCs) have already been demonstrated as ideal candidates for cell therapy in nervous lesions, regarding their high multipotency and the fact they can be easily harvested in the patient himself. After it has been demonstrated that some BMSCs arise from the embryonic neural crest (NC), we compared NC-BMSCs and mesenchymal (M)-BMSCs in vitro, in terms of differenciation abilities and more particularly in terms of neural fate. We then wanted to investigate and compare the potential usefulness of both populations in the context of a neurological pathology. We have validated a MPTP mouse model, mimicking the specific loss of nigral neurons, and started setting up a cell therapy experiment using stereotaxic brain injection of the two types of BMSCs. The survival rate of grafted cells was analyzed as well as their migration or differentiation, and their ability to restore neuronal loss was also observed. Our first results showed that once grafted inside the brain of MPTP mice, NC-BMSCs survive for about a week, staying tightly close to each other the injection track with no visible sign of migration. Afterwards, cells begin to disappear and we only observe a mean survival rate of 1% after 28 days. Looking at the nigrostriatal pathway integrity, neural crest-BMSCs don’t seem to induce any improvement: they don’t differenciate into neural cells, neither replace lost DA cells, and they do not induce any sprouting of surviving DA neurons. While the M-BMSCs graft experiment has to be completed, these first results showed that NC-BMSCs at the stem cell state are not able to restore the lesioned system, and maybe a pre-differenciation step would be required to trigger those cells into a neuronal fate before grafting them in a MPTP-mouse brain.
