Docosahexaenoic acid and arachidonic acid are fundamental supplements for the induction of neuronal differentiation.
Cell replacement therapy is being investigated for the treatment of neurodegenerative disorders. Adult autologous bone marrow-derived mesenchymal stem cells (MSCs) have been induced to differentiate into neuron-like cells harboring a variety of neuronal markers and transcription factors. Neural tissue characteristically contains high proportions of docosahexaenoic acid (DHA) and arachidonic acid (AA). In this study, evaluation of the fatty acid profile of differentiated neuron-like cells revealed a very low level of DHA, similar to that in MSCs but different from typical neurons. Supplementation of the medium with DHA alone resulted in increased levels of DHA but concomitant low levels of AA. However, supplementation with both DHA and AA yielded a fatty acid profile resembling that of neural tissue. It also resulted in enhanced outgrowth of neurite-like processes, hallmarks of neuronal differentiation. These findings demonstrate the essentiality of DHA and AA supplementation in the process of induced neuronal differentiation and have important implications for the development of cell replacement strategies of neural repair.
Kan
Inna
I
Laboratory of Neurosciences, Felsenstein Medical Research Center, Beilinson Campus, Sackler School of Medicine, Tel Aviv University, Petah Tiqwa 49100, Israel.
Melamed
Eldad
E
Offen
Daniel
D
Green
Pnina
P
D016718:Arachidonic Acid / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects*
D005231:Fatty Acids, Unsaturated; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid