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Next-generation Tumor-homing Induced Neural Stem Cells as an Adjuvant to Radiation for the Treatment of Metastatic Lung Cancer.
- Source :
-
Stem cell reviews and reports [Stem Cell Rev Rep] 2022 Oct; Vol. 18 (7), pp. 2474-2493. Date of Electronic Publication: 2022 Apr 19. - Publication Year :
- 2022
-
Abstract
- The spread of non-small cell lung cancer (NSCLC) to the leptomeninges is devastating with a median survival of only a few months. Radiation offers symptomatic relief, but new adjuvant therapies are desperately needed. Spheroidal, human induced neural stem cells (hiNeuroS) secreting the cytotoxic protein, TRAIL, have innate tumoritropic properties. Herein, we provide evidence that hiNeuroS-TRAIL cells can migrate to and suppress growth of NSCLC metastases in combination with radiation. In vitro cell tracking and post-mortem tissue analysis showed that hiNeuroS-TRAIL cells migrate to NSCLC tumors. Importantly, isobolographic analysis suggests that TRAIL with radiation has a synergistic cytotoxic effect on NSCLC tumors. In vivo, mice treated with radiation and hiNeuroS-TRAIL showed significant (36.6%) improvements in median survival compared to controls. Finally, bulk mRNA sequencing analysis showed both NSCLC and hiNeuroS-TRAIL cells showed changes in genes involved in migration following radiation. Overall, hiNeuroS-TRAIL cells +/- radiation have the capacity to treat NSCLC metastases.<br /> (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Subjects :
- Animals
Apoptosis
Cell Line, Tumor
Humans
Mice
RNA, Messenger
TNF-Related Apoptosis-Inducing Ligand genetics
TNF-Related Apoptosis-Inducing Ligand metabolism
TNF-Related Apoptosis-Inducing Ligand pharmacology
Antineoplastic Agents pharmacology
Carcinoma, Non-Small-Cell Lung genetics
Carcinoma, Non-Small-Cell Lung radiotherapy
Lung Neoplasms genetics
Lung Neoplasms radiotherapy
Neural Stem Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2629-3277
- Volume :
- 18
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Stem cell reviews and reports
- Publication Type :
- Academic Journal
- Accession number :
- 35441348
- Full Text :
- https://doi.org/10.1007/s12015-022-10375-3