The morphofunctional properties of induced pluripotent stem cells derived from human skin fibroblasts and differentiated to dopaminergic neurons View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2013-07

AUTHORS

O. S. Lebedeva, M. A. Lagar’kova, S. L. Kiselev, I. V. Mukhina, M. V. Vedunova, O. V. Usova, A. V. Stavrovskaya, N. G. Yamshchikova, E. Yu. Fedotova, I. A. Grivennikov, L. G. Khaspekov, S. N. Illarioshkin

ABSTRACT

A dopamine deficit in the nigrostriatal system is the key neurotransmitter impairment that is responsible for the principal clinical manifestations of Parkinson’s disease. Modern therapeutic methods allow one to alleviate the severity of individual symptoms; however, replacement therapy does not prevent the progression of the neurodegenerative process. For the treatment of Parkinsonism, transplantation of fully functional dopaminergic neurons into the brain is a promising therapeutic approach. In the present study, we prepared induced pluripotent stem cells (IPSCs) by reprogramming them from fibroblasts that were obtained from a skin biopsy of three patients with genetic forms of Parkinson’s disease with mutations in the LRRK2 and PRKN genes. The pluripotency of these cells was verified by expression of the respective transcription factors, including OCT4, SOX2, and others and their ability to differentiate in ecto-, meso-, and endodermal derivatives. Using IPSCs from patients we created dopaminergic neurons that expressed tyrosine hydroxylase and exhibited spontaneous bioelectrical activity when they were grown on a multielectrode array. In rats with a Parkinsonism model induced by toxic 6-OHDA treatment, transplantation of these dopaminergic neurons into the striatum substantially improved motor function and reduced Parkinsonism symptoms. More... »

PAGES

207-214

Identifiers

URI

http://scigraph.springernature.com/pub.10.1134/s1819712413030082

DOI

http://dx.doi.org/10.1134/s1819712413030082

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1035762779


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