Intranasally Administered L-Myc-Immortalized Human Neural Stem Cells Migrate to Primary and Distal Sites of Damage after Cortical Impact and Enhance Spatial Learning
As the success of stem cell-based therapies is contingent on efficient cell delivery to damaged areas, neural stem cells (NSCs) have promising therapeutic potential because they inherently migrate to sites of central nervous system (CNS) damage. To explore the possibility of NSC-based therapy after...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2021/5549381 |
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| author | Margarita Gutova Jeffrey P. Cheng Vikram Adhikarla Lusine Tsaturyan Michael E. Barish Russell C. Rockne Eleni H. Moschonas Corina O. Bondi Anthony E. Kline |
| author_facet | Margarita Gutova Jeffrey P. Cheng Vikram Adhikarla Lusine Tsaturyan Michael E. Barish Russell C. Rockne Eleni H. Moschonas Corina O. Bondi Anthony E. Kline |
| author_sort | Margarita Gutova |
| collection | DOAJ |
| description | As the success of stem cell-based therapies is contingent on efficient cell delivery to damaged areas, neural stem cells (NSCs) have promising therapeutic potential because they inherently migrate to sites of central nervous system (CNS) damage. To explore the possibility of NSC-based therapy after traumatic brain injury (TBI), isoflurane-anesthetized adult male rats received a controlled cortical impact (CCI) of moderate severity (2.8 mm deformation at 4 m/s) or sham injury (i.e., no cortical impact). Beginning 1-week post-injury, the rats were immunosuppressed and 1×106 human NSCs (LM-NS008.GFP.fLuc) or vehicle (VEH) (2% human serum albumen) were administered intranasally (IN) on post-operative days 7, 9, 11, 13, 15, and 17. To evaluate the spatial distributions of the LM-NSC008 cells, half of the rats were euthanized on day 25, one day after completion of the cognitive task, and the other half were euthanized on day 46. 1 mm thick brain sections were optically cleared (CLARITY), and volumes were imaged by confocal microscopy. In addition, LM-NSC008 cell migration to the TBI site by immunohistochemistry for human-specific Nestin was observed at day 39. Acquisition of spatial learning was assessed in a well-established Morris water maze task on six successive days beginning on post-injury day 18. IN administration of LM-NSC008 cells after TBI (TBI+NSC) significantly facilitated spatial learning relative to TBI+VEH rats (p<0.05) and had no effect on sham+NSC rats. Overall, these data indicate that IN-administered LM-NSC008 cells migrate to sites of TBI damage and that their presence correlates with cognitive improvement. Future studies will expand on these preliminary findings by evaluating other LM-NSC008 cell dosing paradigms and evaluating mechanisms by which LM-NSC008 cells contribute to cognitive recovery. |
| format | Article |
| id | doaj-art-8b48aabf33ef4941b4f1114a460aa041 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-8b48aabf33ef4941b4f1114a460aa0412025-08-20T03:37:33ZengWileyStem Cells International1687-966X1687-96782021-01-01202110.1155/2021/55493815549381Intranasally Administered L-Myc-Immortalized Human Neural Stem Cells Migrate to Primary and Distal Sites of Damage after Cortical Impact and Enhance Spatial LearningMargarita Gutova0Jeffrey P. Cheng1Vikram Adhikarla2Lusine Tsaturyan3Michael E. Barish4Russell C. Rockne5Eleni H. Moschonas6Corina O. Bondi7Anthony E. Kline8Department of Developmental & Stem Cell Biology, Beckman Research Institute, City of Hope, Duarte, CA, USAPhysical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USADepartment of Computational and Quantitative Medicine, Division of Mathematical Oncology, Beckman Research Institute, City of Hope, Duarte, CA, USADepartment of Developmental & Stem Cell Biology, Beckman Research Institute, City of Hope, Duarte, CA, USADepartment of Developmental & Stem Cell Biology, Beckman Research Institute, City of Hope, Duarte, CA, USADepartment of Computational and Quantitative Medicine, Division of Mathematical Oncology, Beckman Research Institute, City of Hope, Duarte, CA, USAPhysical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USAPhysical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USAPhysical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USAAs the success of stem cell-based therapies is contingent on efficient cell delivery to damaged areas, neural stem cells (NSCs) have promising therapeutic potential because they inherently migrate to sites of central nervous system (CNS) damage. To explore the possibility of NSC-based therapy after traumatic brain injury (TBI), isoflurane-anesthetized adult male rats received a controlled cortical impact (CCI) of moderate severity (2.8 mm deformation at 4 m/s) or sham injury (i.e., no cortical impact). Beginning 1-week post-injury, the rats were immunosuppressed and 1×106 human NSCs (LM-NS008.GFP.fLuc) or vehicle (VEH) (2% human serum albumen) were administered intranasally (IN) on post-operative days 7, 9, 11, 13, 15, and 17. To evaluate the spatial distributions of the LM-NSC008 cells, half of the rats were euthanized on day 25, one day after completion of the cognitive task, and the other half were euthanized on day 46. 1 mm thick brain sections were optically cleared (CLARITY), and volumes were imaged by confocal microscopy. In addition, LM-NSC008 cell migration to the TBI site by immunohistochemistry for human-specific Nestin was observed at day 39. Acquisition of spatial learning was assessed in a well-established Morris water maze task on six successive days beginning on post-injury day 18. IN administration of LM-NSC008 cells after TBI (TBI+NSC) significantly facilitated spatial learning relative to TBI+VEH rats (p<0.05) and had no effect on sham+NSC rats. Overall, these data indicate that IN-administered LM-NSC008 cells migrate to sites of TBI damage and that their presence correlates with cognitive improvement. Future studies will expand on these preliminary findings by evaluating other LM-NSC008 cell dosing paradigms and evaluating mechanisms by which LM-NSC008 cells contribute to cognitive recovery.http://dx.doi.org/10.1155/2021/5549381 |
| spellingShingle | Margarita Gutova Jeffrey P. Cheng Vikram Adhikarla Lusine Tsaturyan Michael E. Barish Russell C. Rockne Eleni H. Moschonas Corina O. Bondi Anthony E. Kline Intranasally Administered L-Myc-Immortalized Human Neural Stem Cells Migrate to Primary and Distal Sites of Damage after Cortical Impact and Enhance Spatial Learning Stem Cells International |
| title | Intranasally Administered L-Myc-Immortalized Human Neural Stem Cells Migrate to Primary and Distal Sites of Damage after Cortical Impact and Enhance Spatial Learning |
| title_full | Intranasally Administered L-Myc-Immortalized Human Neural Stem Cells Migrate to Primary and Distal Sites of Damage after Cortical Impact and Enhance Spatial Learning |
| title_fullStr | Intranasally Administered L-Myc-Immortalized Human Neural Stem Cells Migrate to Primary and Distal Sites of Damage after Cortical Impact and Enhance Spatial Learning |
| title_full_unstemmed | Intranasally Administered L-Myc-Immortalized Human Neural Stem Cells Migrate to Primary and Distal Sites of Damage after Cortical Impact and Enhance Spatial Learning |
| title_short | Intranasally Administered L-Myc-Immortalized Human Neural Stem Cells Migrate to Primary and Distal Sites of Damage after Cortical Impact and Enhance Spatial Learning |
| title_sort | intranasally administered l myc immortalized human neural stem cells migrate to primary and distal sites of damage after cortical impact and enhance spatial learning |
| url | http://dx.doi.org/10.1155/2021/5549381 |
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