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Low-dose irradiated mesenchymal stromal cells break tumor defensive properties in vivo.
- Source :
-
International journal of cancer [Int J Cancer] 2018 Nov 01; Vol. 143 (9), pp. 2200-2212. Date of Electronic Publication: 2018 Aug 07. - Publication Year :
- 2018
-
Abstract
- Solid tumors, including gliomas, still represent a challenge to clinicians and first line treatments often fail, calling for new paradigms in cancer therapy. Novel strategies to overcome tumor resistance are mainly represented by multi-targeted approaches, and cell vector-based therapy is one of the most promising treatment modalities under development. Here, we show that mouse bone marrow-derived mesenchymal stromal cells (MSCs), when primed with low-dose irradiation (irMSCs), undergo changes in their immunogenic and angiogenic capacity and acquire anti-tumoral properties in a mouse model of glioblastoma (GBM). Following grafting in GL261 glioblastoma, irMSCs migrate extensively and selectively within the tumor and infiltrate predominantly the peri-vascular niche, leading to rejection of established tumors and cure in 29% of animals. The therapeutic radiation dose window is narrow, with effects seen between 2 and 15 Gy, peaking at 5 Gy. A single low-dose radiation decreases MSCs inherent immune suppressive properties in vitro as well as shapes their immune regulatory ability in vivo. Intra-tumorally grafted irMSCs stimulate the immune system and decrease immune suppression. Additionally, irMSCs enhance peri-tumoral reactive astrocytosis and display anti-angiogenic properties. Hence, the present study provides strong evidence for a therapeutic potential of low-dose irMSCs in cancer as well as giving new insight into MSC biology and applications.<br /> (© 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)
- Subjects :
- Animals
Apoptosis
Cell Proliferation
Female
Glioblastoma blood supply
Mesenchymal Stem Cells cytology
Mesenchymal Stem Cells radiation effects
Mice
Mice, Inbred C57BL
Tumor Cells, Cultured
Glioblastoma immunology
Glioblastoma therapy
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0215
- Volume :
- 143
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- International journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 29752716
- Full Text :
- https://doi.org/10.1002/ijc.31599