ORIGINAL ARTICLES  PARKINSON’S DISEASE 

Journal of Neurosurgical Sciences 2003 March;47(1):8-17

Copyright © 2004 EDIZIONI MINERVA MEDICA

lingua: Inglese

Neural stem cells. Biological features and therapeutic potential in Parkinson’s disease

Parati E. A., Bez A., Ponti D., Sala S., Pozzi S., Pagano S. F.

Laboratory of Neurobiology, National Neurological Institute “C. Besta”, Milan, Italy

Aim. Neural ­stem ­cells (NSC) are clon­o­gen­ic ­cells, ­capable of ­self-renew­al and mul­ti­lin­e­age dif­fe­ren­ti­a­tion, ­since, ­under the appro­pri­at­ed experi­men­tal con­di­tions, ­they pro­life­rate indef­i­nite­ly as undif­fer­en­tiat­ed neu­ro­spheres or dif­fer­en­tiate in neu­rons, astro­cy­tes and olig­o­den­droc­y­tes. Parkinson’s dis­ease is a neu­ro­de­gen­er­a­tive dis­or­der char­ac­ter­ized by the pro­gres­sive ­loss of dopam­i­ner­gic neu­rons.
Methods. Here we inves­ti­gat­ed the suit­abil­ity of recent­ly iden­ti­fied and char­ac­ter­ized neu­ro­nal pro­gen­i­tor ­cells at elic­it­ing func­tion­al recov­ery in uni­lat­er­al 6­HODA-­lesioned ­mice. We ­describe here­in ­that intra­stri­a­tal engraft­ment of ­stem ­cell-­derived neu­rons iso­lat­ed ­from the olfac­to­ry ­bulb to ­give ­rise dopam­i­ner­gic-­like neu­rons ­results in ­long last­ing func­tion­al recov­ery in 6­OHDA-­injured ­mice.
Results. Unilateral injec­tion of 6­OHDA result­ed in a pro­gres­sive neu­ro­de­gen­er­a­tion of the ­nigro-stri­a­tal path­way. Likewise, the system­ic admin­is­tra­tion of L-­DOPA in ­these ­mice elic­it­ed a ­marked con­tra­lat­er­al turn­ing ­which was evi­dent 1 ­week ­post, ­increased dur­ing the fol­low­ing ­week and ­than sta­bi­lize through­out the ­time of the experi­ment. Conversely, the intra­stri­a­tal implan­ta­tion of par­tial­ly dif­fer­en­tiat­ed ­stem ­cells at 14 ­days post­le­sion, result­ed in a pro­found ­decrease in L-­DOPA-­induced cir­cling behav­ior; inter­est­ing­ly, the ­effect was evi­dent 1 ­week ­after the engraft­ment and was ­retained dur­ing the fol­low­ing 9 ­weeks. Detailed bio­chem­i­cal and immu­no­his­to­chem­i­cal eval­u­a­tion is cur­rent­ly ­under inves­ti­ga­tion in our labor­a­to­ry.
Conclusion. Our obser­va­tion ­opens new per­spec­tives for the treat­ment of neu­ro­de­gen­er­a­tion in Parkinson’s dis­ease.