Transplanted Human Neural Progenitor Cells Attenuate Motor Dysfunction and Lengthen Longevity in a Rat Model of Ataxia

The spastic Han Wistar (sHW) rat serves as a model for human ataxia presenting symptoms of motor deterioration, weight loss, shortened lifespan, and Purkinje neuron loss. Past studies revealed that human neural progenitor cells (NPCs) improved ataxic symptoms at 20 d posttransplantation in sHW rats....

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Bibliographic Details
Published in:Cell transplantation 2020-01, Vol.29, p.963689720920275-963689720920275
Main Authors: Tierney, Wesley M., Uhlendorf, Toni L., Lemus, Aaron J.J., Ortega, Bianca A., Magaña, Jesse, Ochoa, Jessica, Van Trigt, William, Cruz, Angelica, Kopyov, Alex, Kopyov, Oleg V., Cohen, Randy W.
Format: Article
Language:English
Subjects:
Animal models
Ataxia
Cerebellum
Immunohistochemistry
Life span
Motor activity
Mutants
Neural stem cells
Neurodegenerative diseases
Neuroprotective agents
Open-field behavior
Original
Progenitor cells
Purkinje cells
Spasticity
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Summary:The spastic Han Wistar (sHW) rat serves as a model for human ataxia presenting symptoms of motor deterioration, weight loss, shortened lifespan, and Purkinje neuron loss. Past studies revealed that human neural progenitor cells (NPCs) improved ataxic symptoms at 20 d posttransplantation in sHW rats. In this study, we investigated the fate and longer-term effectiveness of these transplanted NPCs. Rats were placed into four treatment groups: an untreated normal control group (n = 10), an untreated mutant rat control (n = 10), a mutant group that received an injection of dead NPCs (n = 9), and a mutant group that received live NPCs (n = 10). Bilateral cerebellar injections containing 500,000 of either live or dead NPCs were performed on mutant sHW rats at 40 d of age. Motor activity for all mutant rats started to decline in open field testing around day 35. However, at day 45, the live NPC-treated mutants exhibited significant improvements in open field activity. Similar improvements were observed during rotarod testing and weight gain through the completion of the experiments (100 d). Immunohistochemistry revealed few surviving human NPCs in the cerebella of 80- and 100-d-old NPC-treated mutants; while cresyl violet staining revealed that live NPC-treated mutants had significantly more surviving Purkinje neurons compared to mutants that were untreated or received dead NPCs. Direct stereotactic implantation of NPCs alleviated the symptoms of ataxia, acting as a neuroprotectant, supporting future clinical applications of these NPCs in the areas of ataxia as well as other neurodegenerative diseases.
ISSN:0963-6897
1555-3892
DOI:10.1177/0963689720920275