NDLI: Differential pathotropism of non-immortalized and immortalized human neural stem cell lines in a focal demyelination model

Content Provider	Springer Nature Link
Author	Ferrari, Daniela Zalfa, Cristina Rota dari, Laura Gelati, Maurizio Carlessi, Luigi Delia, Domenico Vescovi, Angelo Luigi Filippis, Lidia
Copyright Year	2011
Abstract	Cell therapy is reaching the stage of phase I clinical trials for post-traumatic, post-ischemic, or neurodegenerative disorders, and the selection of the appropriate cell source is essential. In order to assess the capacity of different human neural stem cell lines (hNSC) to contribute to neural tissue regeneration and to reduce the local inflammation after an acute injury, we transplanted GMP-grade non-immortalized hNSCs and v-myc (v-IhNSC), c-myc T58A (T-IhNSC) immortalized cells into the corpus callosum of adult rats after 5 days from focal demyelination induced by lysophosphatidylcholine. At 15 days from transplantation, hNSC and T-IhNSC migrated to the lesioned area where they promoted endogenous remyelination and differentiated into mature oligodendrocytes, while the all three cell lines were able to integrate in the SVZ. Moreover, where demyelination was accompanied by an inflammatory reaction, a significant reduction of microglial cells’ activation was observed. This effect correlated with a differential migratory pattern of transplanted hNSC and IhNSC, significantly enhanced in the former, thus suggesting a specific NSC-mediated immunomodulatory effect on the local inflammation. We provide evidence that, in the subacute phase of a demyelination injury, different human immortalized and non-immortalized NSC lines, all sharing homing to the stem niche, display a differential pathotropism, both through cell-autonomous and non-cell autonomous effects. Overall, these findings promote IhNSC as an inexhaustible cell source for large-scale preclinical studies and non-immortalized GMP grade hNSC lines as an efficacious, safe, and reliable therapeutic tool for future clinical applications.
Starting Page	1193
Ending Page	1210
Page Count	18
File Format	PDF
ISSN	1420682X
Journal	Cellular and Molecular Life Sciences
Volume Number	69
Issue Number	7
e-ISSN	14209071
Language	English
Publisher	SP Birkhäuser Verlag Basel
Publisher Date	2011-11-11
Publisher Place	Basel
Access Restriction	Subscribed
Subject Keyword	Fetal Human Neural Stem Cells Re-myelination Transplantation Lysophosphatidylcoline Immunomodulation Biochemistry Cell Biology Biomedicine general Life Sciences
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology Molecular Medicine Pharmacology Cellular and Molecular Neuroscience

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