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

Autor: O. S. Lebedeva, E. Yu. Fedotova, Irina Mukhina, M. V. Vedunova, I. A. Grivennikov, Maria A. Lagarkova, Sergey L. Kiselev, A. V. Stavrovskaya, Sergey N. Illarioshkin, Leonid G. Khaspekov, N. G. Yamshchikova, O. V. Usova
Rok vydání: 2013
Předmět:
Zdroj: Neurochemical Journal. 7:207-214
ISSN: 1819-7132
1819-7124
DOI: 10.1134/s1819712413030082
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: