Back to Search
Start Over
Therapeutic potential of mesenchymal stem cells producing IFN-α in a mouse melanoma lung metastasis model
- Publication Year :
- 2008
-
Abstract
- Adult stem cells represent a potential source for cell-based therapy of cancer. The present study evaluated the potential of bone marrow-derived mesenchymal stem cells (MSC), genetically modified to express interferon (IFN)-α, for the treatment of lung metastasis in an immunocompetent mouse model of metastatic melanoma. A recombinant adeno-associated virus (rAAV) 6 vector encoding IFN-α was used to transduce mouse bone marrow-derived MSC ex vivo. Expression and bioactivity of the transgenic protein from rAAV-transduced MSC were confirmed prior to in vivo studies. A lung metastasis model of melanoma was developed by i.v. injection of B16F10 cells into 8-week-old C57BL/6 mice. Ten days later, MSC transduced with rAAV-IFN-α or green fluorescent protein were intravenously injected. One cohort of mice was sacrificed to determine the effects of the therapy at an earlier time point, and another cohort was observed for long-term survival. Results indicated that systemic administration of MSC producing IFN-α reduced the growth of B16F10 melanoma cells and significantly prolonged survival. Immunohistochemistry analysis of the tumors from MSC-IFN-α-treated animals indicated an increase in apoptosis and a decrease in proliferation and blood vasculature. These data demonstrate the potential of adult MSC constitutively producing IFN-α to reduce the growth of lung metastasis in melanoma. Disclosure of potential conflicts of interest is found at the end of this article.
- Subjects :
- Lung Neoplasms
Cell
Melanoma, Experimental
Apoptosis
Biology
Mesenchymal Stem Cell Transplantation
Article
Cell Line
Mice
Interferon
medicine
Animals
Humans
Cell Proliferation
Neovascularization, Pathologic
Melanoma
Mesenchymal stem cell
Cancer
Mesenchymal Stem Cells
Cell Biology
Dependovirus
medicine.disease
Recombinant Proteins
Mice, Inbred C57BL
medicine.anatomical_structure
Cell culture
Immunology
Interferon Type I
Cancer research
Molecular Medicine
Female
Ex vivo
Neoplasm Transplantation
Developmental Biology
medicine.drug
Adult stem cell
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....2a9a4ca45615fd5c97f7802ca54bfd6c