Effect of Cell Genome Editing on the Outcome of Neurotransplantation in Experimental Parkinsonism

• DOI: 10.17691/stm2017.9.4.01
• Publication Date: 2017-12-28T08:58:29Z
• Authors: A.V. Stavrovskaya; E.V. Novosadova; A.S. Olshansky; N.G. Yamshchikova; A.S. Gushchina; E.L. Arsenyeva; I.A. Grivennikov; S.N. Illarioshkin
• Keywords: 0301 basic medicine; 03 medical and health sciences

The aim of the study was to evaluate effect genome editing on outcome experimental transplantation neuronal precursors obtained from a patient with hereditary form Parkinson's disease.Materials and Methods.Parkinsonian syndrome modeled in Wistar rats (n=24) by unilateral administration (into substantia nigra) neurotoxin 6-hydroxydopamine, that selectively destroy dopaminergic neurons.The neural progenitors were differentiated induced pluripotent stem cells (iPSCs) derived PARK8 disease carrying G2019S mutation LRRK2 gene.In two series experiments, containing mutated gene isogenic "normalized" (that underwent using artificial endonuclease system CRISP/Cas9) used for neurotransplantation.The transplanted via injection into brain striatum rats.We then monitored changes behavior animals open field test passive avoidance response (PAR) test.The data processed Statistica 7.0 software single-factor analysis variance (ANOVA).Results.The rat led gradual restoration motor activity both groups, i.e., those either mutant or cells.In PAR test, failed reproduce conditioned responses, whereas able responses way similar intact rats.The latent period before entering dark box differed between groups high degree statistical significance. Conclusion.The confirms possibility correcting cognitive impairments parkinsonian replenishing pool neurons produced iPSCs somatic (fibroblasts).Using correct causal significantly improves treatment results.This study, therefore, provides rationale further development this promising technique its eventual use patients genetically determined forms disease.