title: Intrastriatal Grafting of Chromospheres: Survival and Functional Effects in the 6-OHDA Rat Model of Parkinson's Disease.
abstract: Cell replacement therapy in Parkinson's disease (PD) aims at re-establishing dopamine neurotransmission in the striatum by grafting dopamine-releasing cells. Chromaffin cell (CC) grafts produce some transitory improvements of functional motor deficits in PD animal models, and have the advantage of allowing autologous transplantation. However, CC grafts have exhibited low survival, poor functional effects and dopamine release compared to other cell types. Recently, chromaffin progenitor-like cells were isolated from bovine and human adult adrenal medulla. Under low-attachment conditions, these cells aggregate and grow as spheres, named chromospheres. Here, we found that bovine-derived chromosphere-cell cultures exhibit a greater fraction of cells with a dopaminergic phenotype and higher dopamine release than CC. Chromospheres grafted in a rat model of PD survived in 57% of the total grafted animals. Behavioral tests showed that surviving chromosphere cells induce a reduction in motor alterations for at least 3 months after grafting. Finally, we found that compared with CC, chromosphere grafts survive more and produce more robust and consistent motor improvements. However, further experiments would be necessary to determine whether the functional benefits induced by chromosphere grafts can be improved, and also to elucidate the mechanisms underlying the functional effects of the grafts.
authors.affiliation: Instituto de Fisiología Celular, Departamento de Neuropatología Molecular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Ciudad de México, México.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Boronat-García
authors.affiliation: Instituto de Fisiología Celular, Departamento de Neuropatología Molecular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Ciudad de México, México.
authors.forename: Marcela
authors.initials: M
authors.lastname: Palomero-Rivero
authors.affiliation: Instituto de Fisiología Celular, Departamento de Neuropatología Molecular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Ciudad de México, México.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Guerra-Crespo
authors.affiliation: Instituto de Fisiología Celular, Departamento de Neuropatología Molecular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Ciudad de México, México.
authors.forename: Diana
authors.initials: D
authors.lastname: Millán-Aldaco
authors.affiliation: Instituto de Fisiología Celular, Departamento de Neuropatología Molecular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Ciudad de México, México.
authors.forename: René
authors.initials: R
authors.lastname: Drucker-Colín
mesh_terms: D000818:Animals; D002417:Cattle; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D019439:Chromaffin Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D008297:Male; D009043:Motor Activity; D017072:Neostriatum / Q000378:metabolism*; D016627:Oxidopamine / Q000494:pharmacology*; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation; D016019:Survival Analysis
chemical_list: D016627:Oxidopamine; D004298:Dopamine