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- Title
The use of hypoxic cultured mesenchymal stem cell for oncolytic virus therapy.
- Authors
Huang, Y-F; Chen, M-J; Wu, M-H; Hung, S-C
- Abstract
The safety of oncolytic viruses, such as conditionally repllcative adenoviruses (CRAds), has been validated in clinical trials for cancer therapy. Their antitumor efficacy is limited by the presence of preexisting neutralizing antibodies (NAbs). Mesenchymal stem cells (MSCs) are attractive as a cellular vehicle to carry antitumor agents, not only because they are easily obtained and expanded to great numbers in vitro, but also because of their ability to migrate and engraft to tumors. MSCs expanded under hypoxic conditions decrease in replicative senescence and increase in proliferation capacity and differentiation potentials. However It remains to be clarified whether these hypoxic MSCs also are good carriers for the delivery of CRAds to tumor cells in the presence of NAbs. This study firstly demonstrated hypoxic MSCs with an increased ability to migrate toward tumors through the upregulatlon of chemokine receptors, such as CXCR4 and CX3CR1. It is then demonstrated that hypoxic MSCs has the capacity to carry CRAds, without inducing apoptosis, for up to one week. Using an in vitro coculture with human colon cancer cells and with intraperitoneally (I.p.) and subcutaneously (s.c.) developed human colon cancer xenografts, It Is demonstrated that hypoxic MSCs are able to protect CRAds from attack by NAbs, thereby successfully delivering them to the target tumor cells. These results show that hypoxic MSCs can serve as cell carriers for CRAds and may help to develop new strategies against cancer.
- Subjects
HYPOXEMIA; MESENCHYMAL stem cells; VIROTHERAPY; ADENOVIRUSES; CLINICAL trials; CANCER treatment; ANTINEOPLASTIC agents; DRUG efficacy; THERAPEUTICS
- Publication
Cancer Gene Therapy, 2013, Vol 20, Issue 5, p308
- ISSN
0929-1903
- Publication type
Article
- DOI
10.1038/cgt.2013.22