The role of HIF-1 alpha in the localization of embryonic stem cells with respect to hypoxia within teratomas

In embryonic stem (ES) cell tumors, the hypoxia-inducible transcription factor, HIF- 1[alpha], has been shown to be a tumor suppressor, and HIF-1[alpha]-expressing cells have been shown to localize preferentially in vivo to regions near tumor vasculature. These differences were proposed to be due to increased hypoxia-induced apoptosis and growth arrest of HIF-1[alpha]-expressing ES cells. This thesis presents a careful investigation into the localization of ES cells in vitro and in vivo with respect to hypoxia. A sandwich culture system was utilized in which controlled gradients of oxygen and nutrients are developed in the vicinity of the tumor cells. A diffusion-consumption model was utilized to predict the oxygen and glucose concentration profiles within the system. Oxygen and glucose consumption rates were measured and used as inputs into the model, and the concentration profiles were found to depend on a single experimental parameter, the cell density within the system. The optimum cell density was found in which stable, measurable oxygen gradients develop over 2-3 mm. The model demonstrated excellent agreement between the predicted oxygen concentration profiles and experimentally determined oxygen gradients. In vitro, there was no difference in localization with respect to hypoxia between tumor cells expressing or lacking HIF-1[alpha].

Department dc:contributor.department

Harvard University--MIT Division of Health Sciences and Technology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2005

Author dc:creator

• Cochran, David M., Ph. D. Massachusetts Institute of Technology

Advisor dc:contributor.advisor

• Rakesh K. Jain.

• Harvard University--MIT Division of Health Sciences and Technology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/33841
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/33841

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/33841