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Tumor stroma engraftment of gene-modified mesenchymal stem cells as anti-tumor therapy against ovarian cancer.
- Source :
-
Cytotherapy [Cytotherapy] 2013 Jan; Vol. 15 (1), pp. 20-32. - Publication Year :
- 2013
-
Abstract
- Background Aims: Many ovarian cancers originate from ovarian surface epithelium, where they develop from cysts intermixed with stroma. The stromal layer is critical to the progression and survival of the neoplasm and consequently is recruited into the tumor microenvironment.<br />Methods: Using both syngeneic mouse tumors (ID8-R) and human xenograft (OVCAR3, SKOV3) tumor models, we first confirmed that intraperitoneally injected circulating mesenchymal stem cells (MSCs) could target, preferentially engraft and differentiate into α-smooth muscle actin-positive myofibroblasts, suggesting their role as "reactive stroma" in ovarian carcinoma development and confirming their potential as a targeted delivery vehicle for the intratumoral production of interferon-β (IFN-β). Mice with ovarian carcinomas then received weekly intraperitoneal injections of IFN-β expressing MSCs.<br />Results: Intraperitoneal injections of IFN-β expressing MSCs resulted in complete eradication of tumors in 70% of treated OVCAR3 mice (P = 0.004) and an increased survival of treated SKOV3 mice compared with controls (P = 0.01). Similar tumor growth control was observed using murine IFN-β delivered by murine MSCs in ID8-R ovarian carcinoma. As a potential mechanism of tumor killing, MSCs produced IFN-β-induced caspase-dependent tumor cell apoptosis.<br />Conclusions: Our results demonstrate that ovarian carcinoma engrafts MSCs to participate in myofibrovascular networks and that IFN-β produced by MSCs intratumorally modulates tumor kinetics, resulting in prolonged survival.<br /> (Published by Elsevier Inc.)
- Subjects :
- Animals
Cell Line, Tumor
Cell Proliferation
Cells, Cultured
Female
Genetic Therapy methods
Humans
Immunohistochemistry
Interferon-beta therapeutic use
Male
Mice
Mice, Inbred C57BL
Xenograft Model Antitumor Assays
Mesenchymal Stem Cells cytology
Mesenchymal Stem Cells drug effects
Ovarian Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1477-2566
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cytotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 23260083
- Full Text :
- https://doi.org/10.1016/j.jcyt.2012.10.003