Human dental pulp stem cells protect mouse dopaminergic neurons against MPP+ or rotenone.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive death of substantia nigra dopaminergic neurons that results in a regional loss of striatal dopamine (DA) levels. Dental pulp contains ex vivo-expandable cells called dental pulp stem cells (DPSCs), with the capacity to differentiate into multiple cell lineages. More interestingly, due to their embryonic origin, DPSCs express neurotrophic factors such as brain-derived neurotrophic factor, nerve growth factor and glial cell-derived neurotrophic factor. The aim of the present study was to investigate the neuroprotective effects of DPSCs against MPP+ (2.5, 5, and 10 μM) and rotenone (0.25, 0.5 and 1 μM) in an in vitro model of PD, using an indirect co-culture system with mesencephalic cell cultures. When mesencephalic cultures were challenged with MPP+ or rotenone, in the presence of DPSCs a statistically significant protective effect was observed at all the tested doses in terms of DA uptake. DPSCs protective effect on DA neurons was also confirmed by immunocytochemistry: an increased number of spared tyrosine hydroxylase (TH)+ cells was observed in co-culture conditions compared to controls, and neurons showed longer processes in comparison with mesencephalic cells grown without DPSCs. In conclusion, the co-culture with DPSCs significantly attenuated MPP+ or rotenone-induced toxicity in primary cultures of mesencephalic neurons. Considering that the direct contact between the two cell types was prevented, it can be speculated that neuroprotection could be due to soluble factors such as BDNF and NGF, released by DPSCs. Blocking BDNF and NGF with neutralizing antibodies, the neuroprotecting effect of DPSCs was completely abolished. Therefore DPSCs can be viewed as possible candidates for studies on cell-based therapy in neurodegenerative disorders.
Nesti
Claudia
C
RRMR/CUCCS (Rete Regionale di Medicina Rigenerativa/Center for the Clinical Use of Stem Cells), Italy; Stella Maris Scientific Institute, Pisa, Italy.
Pardini
Carla
C
Barachini
Serena
S
D'Alessandro
Delfo
D
Siciliano
Gabriele
G
Murri
Luigi
L
Petrini
Mario
M
Vaglini
Francesca
F
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D018920:Coculture Techniques / Q000379:methods; D003782:Dental Pulp / Q000166:cytology*; D004298:Dopamine / Q000378:metabolism*; D004622:Embryo, Mammalian; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008636:Mesencephalon / Q000166:cytology; D051379:Mice; D020932:Nerve Growth Factor / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D011247:Pregnancy; D012402:Rotenone / Q000633:toxicity*; D013234:Stem Cells / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D055815:Young Adult
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009498:Neurotoxins; D012402:Rotenone; D020932:Nerve Growth Factor; D014446:Tyrosine 3-Monooxygenase; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine