| Autor: |
Xiang Zeng, Alexander E. Ropper, Zaid Aljuboori, Dou Yu, Theodore W. Teng, Serdar Kabatas, Esteban Usuga, Jamie E. Anderson, Yang D. Teng |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Cells, Vol 13, Iss 18, p 1522 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2073-4409 |
| DOI: |
10.3390/cells13181522 |
| Popis: |
Intramedullary spinal cord glioblastoma (ISCG) is lethal due to lack of effective treatment. We previously established a rat C6-ISCG model and the antitumor effect of F3.CD-TK, an hNSC line expressing CD and TK, via producing cytocidal 5FU and GCV-TP. However, the neurotherapeutic potential of this hNSC approach has remained uninvestigated. Here for the first time, cultured F3.CD-TK cells were found to have a markedly higher oncolytic effect, which was GJIC-dependent, and BDNF expression but less VEGF secretion than F3.CD. In Rowett athymic rats, F3.CD-TK (1.5 × 106 cells/10 µL × 2), injected near C6-ISCG (G55 seeding 7 days earlier: 10 K/each) and followed by q.d. (×5/each repeat; i.p.) of 5FC (500 mg/kg/5 mL/day) and GCV (25 mg/kg/1 mL/day), robustly mitigated cardiorespiratory, locomotor, and sensory deficits to improve neurofunction and overall survival compared to animals receiving either F3.CD or F3.CD-TK+F3.CD debris formula. The F3.CD-TK regimen exerted greater tumor penetration and neural inflammation/immune modulation, reshaped C6-ISCG topology to increase the tumor’s surface area/volume ratio to spare/repair host axons (e.g., vGlut1+ neurites), and had higher post-prodrug donor self-clearance. The multimodal data and mechanistic leads from this proof-of-principle study suggest that the overall stronger anti-ISCG benefit of our hNSC-based GDEPT is derived from its concurrent oncolytic and neurotherapeutic effects. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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