Transplantation of Human Neural Progenitor Cells Reveals Structural and Functional Improvements in the Spastic Han-Wistar Rat Model of Ataxia
The use of regenerative medicine to treat nervous system disorders like ataxia has been proposed to either replace or support degenerating neurons. In this study, we assessed the ability of human neural progenitor cells (hNPCs) to repair and restore the function of dying neurons within the spastic H...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2017-11-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/0963689717723637 |
| _version_ | 1828465361945624576 |
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| author | Ruslan L. Nuryyev Toni L. Uhlendorf Wesley Tierney Suren Zatikyan Oleg Kopyov Alex Kopyov Jessica Ochoa William Van Trigt Cindy S. Malone Randy W. Cohen |
| author_facet | Ruslan L. Nuryyev Toni L. Uhlendorf Wesley Tierney Suren Zatikyan Oleg Kopyov Alex Kopyov Jessica Ochoa William Van Trigt Cindy S. Malone Randy W. Cohen |
| author_sort | Ruslan L. Nuryyev |
| collection | DOAJ |
| description | The use of regenerative medicine to treat nervous system disorders like ataxia has been proposed to either replace or support degenerating neurons. In this study, we assessed the ability of human neural progenitor cells (hNPCs) to repair and restore the function of dying neurons within the spastic Han-Wistar rat (sHW), a model of ataxia. The sHW rat suffers from neurodegeneration of specific neurons, including cerebellar Purkinje cells and hippocampal CA3 pyramidal cells leading to the observed symptoms of forelimb tremor, hind-leg rigidity, gait abnormality, motor incoordination, and a shortened life span. To alleviate the symptoms of neurodegeneration and to replace or augment dying neurons, neuronal human progenitor cells were implanted into the sHW rats. At 30 d of age, male sHW mutant rats underwent subcutaneous implantation of an Alzet osmotic pump that infused cyclosporine (15 mg/kg/d) used to suppress the rat’s immune system. At 40 d, sHW rats received bilateral injections (500,000 cells in 5 µL media) of live hNPCs, dead hNPCs, live human embryonic kidney cells, or growth media either into the cerebellar cortex or into the hippocampus. To monitor results, motor activity scores (open-field testing) and weights of the animals were recorded weekly. The sHW rats that received hNPC transplantation into the cerebellum, at 60 d of age, displayed significantly higher motor activity scores and sustained greater weights and longevities than control-treated sHW rats or any hippocampal treatment group. In addition, cerebellar histology revealed that the transplanted hNPCs displayed signs of migration and signs of neuronal development in the degenerated Purkinje cell layer. This study revealed that implanted human progenitor cells reduced the ataxic symptoms in the sHW rat, identifying a future clinical use of these progenitor cells against ataxia and associated neurodegenerative diseases. |
| first_indexed | 2024-12-11T03:31:27Z |
| format | Article |
| id | doaj.art-3d78eecc73714e53b5092f2b2a69e96a |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-11T03:31:27Z |
| publishDate | 2017-11-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-3d78eecc73714e53b5092f2b2a69e96a2022-12-22T01:22:23ZengSAGE PublishingCell Transplantation0963-68971555-38922017-11-012610.1177/0963689717723637Transplantation of Human Neural Progenitor Cells Reveals Structural and Functional Improvements in the Spastic Han-Wistar Rat Model of AtaxiaRuslan L. Nuryyev0Toni L. Uhlendorf1Wesley Tierney2Suren Zatikyan3Oleg Kopyov4Alex Kopyov5Jessica Ochoa6William Van Trigt7Cindy S. Malone8Randy W. Cohen9 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 Department of Biology, California State University, Northridge, CA, USA Department of Biology, California State University, Northridge, CA, USA The use of regenerative medicine to treat nervous system disorders like ataxia has been proposed to either replace or support degenerating neurons. In this study, we assessed the ability of human neural progenitor cells (hNPCs) to repair and restore the function of dying neurons within the spastic Han-Wistar rat (sHW), a model of ataxia. The sHW rat suffers from neurodegeneration of specific neurons, including cerebellar Purkinje cells and hippocampal CA3 pyramidal cells leading to the observed symptoms of forelimb tremor, hind-leg rigidity, gait abnormality, motor incoordination, and a shortened life span. To alleviate the symptoms of neurodegeneration and to replace or augment dying neurons, neuronal human progenitor cells were implanted into the sHW rats. At 30 d of age, male sHW mutant rats underwent subcutaneous implantation of an Alzet osmotic pump that infused cyclosporine (15 mg/kg/d) used to suppress the rat’s immune system. At 40 d, sHW rats received bilateral injections (500,000 cells in 5 µL media) of live hNPCs, dead hNPCs, live human embryonic kidney cells, or growth media either into the cerebellar cortex or into the hippocampus. To monitor results, motor activity scores (open-field testing) and weights of the animals were recorded weekly. The sHW rats that received hNPC transplantation into the cerebellum, at 60 d of age, displayed significantly higher motor activity scores and sustained greater weights and longevities than control-treated sHW rats or any hippocampal treatment group. In addition, cerebellar histology revealed that the transplanted hNPCs displayed signs of migration and signs of neuronal development in the degenerated Purkinje cell layer. This study revealed that implanted human progenitor cells reduced the ataxic symptoms in the sHW rat, identifying a future clinical use of these progenitor cells against ataxia and associated neurodegenerative diseases.https://doi.org/10.1177/0963689717723637 |
| spellingShingle | Ruslan L. Nuryyev Toni L. Uhlendorf Wesley Tierney Suren Zatikyan Oleg Kopyov Alex Kopyov Jessica Ochoa William Van Trigt Cindy S. Malone Randy W. Cohen Transplantation of Human Neural Progenitor Cells Reveals Structural and Functional Improvements in the Spastic Han-Wistar Rat Model of Ataxia Cell Transplantation |
| title | Transplantation of Human Neural Progenitor Cells Reveals Structural and Functional Improvements in the Spastic Han-Wistar Rat Model of Ataxia |
| title_full | Transplantation of Human Neural Progenitor Cells Reveals Structural and Functional Improvements in the Spastic Han-Wistar Rat Model of Ataxia |
| title_fullStr | Transplantation of Human Neural Progenitor Cells Reveals Structural and Functional Improvements in the Spastic Han-Wistar Rat Model of Ataxia |
| title_full_unstemmed | Transplantation of Human Neural Progenitor Cells Reveals Structural and Functional Improvements in the Spastic Han-Wistar Rat Model of Ataxia |
| title_short | Transplantation of Human Neural Progenitor Cells Reveals Structural and Functional Improvements in the Spastic Han-Wistar Rat Model of Ataxia |
| title_sort | transplantation of human neural progenitor cells reveals structural and functional improvements in the spastic han wistar rat model of ataxia |
| url | https://doi.org/10.1177/0963689717723637 |
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