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....
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2020-04-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/0963689720920275 |
| _version_ | 1828907504606642176 |
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| author | Wesley M. Tierney Toni L. Uhlendorf Aaron J.J. Lemus Bianca A. Ortega Jesse Magaña Jessica Ochoa William Van Trigt Angelica Cruz Alex Kopyov Oleg V. Kopyov Randy W. Cohen |
| author_facet | Wesley M. Tierney Toni L. Uhlendorf Aaron J.J. Lemus Bianca A. Ortega Jesse Magaña Jessica Ochoa William Van Trigt Angelica Cruz Alex Kopyov Oleg V. Kopyov Randy W. Cohen |
| author_sort | Wesley M. Tierney |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T17:53:46Z |
| format | Article |
| id | doaj.art-f98e01d0561b4ba7be40a22ae64194ad |
| institution | Directory Open Access Journal |
| issn | 1555-3892 |
| language | English |
| last_indexed | 2024-12-13T17:53:46Z |
| publishDate | 2020-04-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-f98e01d0561b4ba7be40a22ae64194ad2022-12-21T23:36:25ZengSAGE PublishingCell Transplantation1555-38922020-04-012910.1177/0963689720920275Transplanted Human Neural Progenitor Cells Attenuate Motor Dysfunction and Lengthen Longevity in a Rat Model of AtaxiaWesley M. Tierney0Toni L. Uhlendorf1Aaron J.J. Lemus2Bianca A. Ortega3Jesse Magaña4Jessica Ochoa5William Van Trigt6Angelica Cruz7Alex Kopyov8Oleg V. Kopyov9Randy W. Cohen10 Department of Biology, California State University, Northridge, CA, USA Department of Biology, California State University, Northridge, CA, USA Department of Biology, California State University, Northridge, CA, USA Department of Biology, California State University, Northridge, CA, USA Department of Biology, California State University, Northridge, CA, USA Celavie Biosciences, LLC, Oxnard, CA, USA Celavie Biosciences, LLC, Oxnard, CA, USA Celavie Biosciences, LLC, Oxnard, CA, USA Celavie Biosciences, LLC, Oxnard, CA, USA Celavie Biosciences, LLC, Oxnard, CA, USA Department of Biology, California State University, Northridge, CA, USAThe 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.https://doi.org/10.1177/0963689720920275 |
| spellingShingle | Wesley M. Tierney Toni L. Uhlendorf Aaron J.J. Lemus Bianca A. Ortega Jesse Magaña Jessica Ochoa William Van Trigt Angelica Cruz Alex Kopyov Oleg V. Kopyov Randy W. Cohen Transplanted Human Neural Progenitor Cells Attenuate Motor Dysfunction and Lengthen Longevity in a Rat Model of Ataxia Cell Transplantation |
| title | Transplanted Human Neural Progenitor Cells Attenuate Motor Dysfunction and Lengthen Longevity in a Rat Model of Ataxia |
| title_full | Transplanted Human Neural Progenitor Cells Attenuate Motor Dysfunction and Lengthen Longevity in a Rat Model of Ataxia |
| title_fullStr | Transplanted Human Neural Progenitor Cells Attenuate Motor Dysfunction and Lengthen Longevity in a Rat Model of Ataxia |
| title_full_unstemmed | Transplanted Human Neural Progenitor Cells Attenuate Motor Dysfunction and Lengthen Longevity in a Rat Model of Ataxia |
| title_short | Transplanted Human Neural Progenitor Cells Attenuate Motor Dysfunction and Lengthen Longevity in a Rat Model of Ataxia |
| title_sort | transplanted human neural progenitor cells attenuate motor dysfunction and lengthen longevity in a rat model of ataxia |
| url | https://doi.org/10.1177/0963689720920275 |
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