Session Information
Date: Monday, September 23, 2019
Session Title: Gene and Cell-Based Therapies
Session Time: 1:45pm-3:15pm
Location: Les Muses Terrace, Level 3
Objective: To perform an in-depth analysis of the effects of transplanting neural stems cells in Parkinsonian mice.
Background: Parkinson´s disease (PD) is the second most common neurodegenerative disease in the world and the most common motor movement disorder. PD is characterized by the impairment and death of dopaminergic neurons (DAn) in the Substantia Nigra pars compacta (SNpc). Cell replacement therapy holds the most promise in the treatment of PD; therefore, we studied an experimental stem cell therapy in a PD rodent model.
Method: Adult (5 month-old) and middle-aged (12 month-old) C57BL/6JRccHsd male mice were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and subsequently transplanted with human ventral mesencephalic hVM1 clone 32 human neural stem cells, or buffer, in the left striatum. Mice were sacrificed four months post-transplant.
Results: Tyrosine hydroxylase (TH) fiber loss in the striatum and DAn loss in the SNpc of adult mice was prevented by stem cell transplantation, while TH neurodegeneration in middle-aged mice was prevented only in the SNpc and not the striatum. Adult stem cell-treated mice showed similar open field test behavior to that of controls, but middle-aged stem cell-treated mice did not. All MPTP-treated animals showed higher levels of inflammation in the striatum and SNpc compared to control mice. Neurogenesis in the subgranular zone, studied via doublecortin immunostaining, was improved in stem cell-treated adult, but not middle-aged, mice.
Conclusion: Transplantation of hVM1 clone 32 human neural stem cells in adult and middle-aged PD mice have different outcomes in terms of dopamine loss and recovery in the striatum and SNpc, behavior, and neurogenesis, with the adult stem cell-treated mice showing significant improvements in all of these aspects. This study stresses the importance of the age of recipient and the stage of PD progression when receiving a transplant.
References: 1. Ramos-Moreno T, Lendínez JG, Pino-Barrio MJ, del Arco A, Martínez-Serrano A. 2012. Clonal Human Fetal Ventral Mesencephalic Dopaminergic Neuron Precursors for Cell Therapy Research. PLoS ONE, 7 (12): e52714. doi:10.1371/journal.pone.0052714.
To cite this abstract in AMA style:
A. Nelke, S. García-López, A. Martínez-Serrano, M. Pérez Pereira. Differential effects of stem cell therapy in adult and middle-aged Parkinsonian mice [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/differential-effects-of-stem-cell-therapy-in-adult-and-middle-aged-parkinsonian-mice/. Accessed June 15, 2025.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/differential-effects-of-stem-cell-therapy-in-adult-and-middle-aged-parkinsonian-mice/