Related Experiment Video
Updated: May 12, 2026
Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant
Published on: May 27, 2011
The use of hypoxic cultured mesenchymal stem cell for oncolytic virus therapy
1Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, and Mackay Memorial Hospital, Taipei, Taiwan.
Abstract:
The safety of oncolytic viruses, such as conditionally replicative 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 upregulation 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.
Insights
Hypoxic mesenchymal stem cells (MSCs) effectively deliver oncolytic adenoviruses (CRAds) to tumors, overcoming neutralizing antibodies. These modified MSCs offer a promising strategy for enhanced cancer therapy.
Area of Science:
- Oncolytic virotherapy
- Cancer immunotherapy
- Cell-based drug delivery
Background:
- Oncolytic viruses, like CRAds, show cancer therapy promise but are limited by neutralizing antibodies (NAbs).
- Mesenchymal stem cells (MSCs) are potential carriers for antitumor agents due to tumor-homing and expansion capabilities.
- Hypoxic expansion of MSCs enhances their proliferation and differentiation, but their efficacy as CRAd carriers in NAbs presence is unclear.
Purpose of the Study:
- To investigate the potential of hypoxic MSCs as carriers for oncolytic adenoviruses (CRAds) in the presence of neutralizing antibodies (NAbs).
- To assess the migration, CRAd-carrying capacity, and protective effects of hypoxic MSCs against NAbs for targeted cancer therapy.
Main Methods:
- Enhanced migration of hypoxic MSCs towards tumors via upregulated chemokine receptors (CXCR4, CX3CR1).
- Assessment of hypoxic MSCs' capacity to carry CRAds for up to one week without inducing apoptosis.
- In vitro and in vivo (xenograft models) evaluation of hypoxic MSCs delivering CRAds to colon cancer cells, assessing protection against NAbs.
Main Results:
- Hypoxic MSCs exhibited enhanced migration towards tumor sites.
- Hypoxic MSCs successfully carried CRAds for an extended period without significant apoptosis.
- Hypoxic MSCs protected CRAds from NAbs, enabling effective delivery to colon cancer cells in vitro and in vivo.
Conclusions:
- Hypoxic MSCs demonstrate improved migratory and tumor-homing capabilities.
- Hypoxic MSCs serve as effective carriers for oncolytic adenoviruses, shielding them from neutralizing antibodies.
- This study supports the development of hypoxic MSCs as a novel cell-based delivery system for enhanced oncolytic virotherapy in cancer treatment.
Related Concept Videos
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
01:19Mesenchymal Stem Cells
01:21Stem Cell Therapy for Tissue Regeneration
Types of Stem Cells used in Stem Cell Therapy
The two main cell types that...
01:17Stem Cell Culture