Genetically Altered Cells for low pO2 Environments

University Of Iowa, Iowa City IA

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Abstract

DESCRIPTION (Verbatim from the applicant's abstract) The use of transplanted cells to aid in combating diseases has been going on for some time. This concept has ranged from whole organ transplants to tissue transplants. But in most cases, immunosuppressing drug therapy must accompany the transplant to prevent rejection. Although these measures have been successful in some cases, the requirement of various immunosuppressive drugs to prevent rejection of these transplanted cells exposes these patients to a wide variety of serious complications including cancer, infection, renal failure and osteoporosis. As an alternative, biocompatible polymers have been used to protect the transplanted cells from the immune response. However this protection comes at a costs. This additional material adds significant mass transfer resistance to critical nutrients such as oxygen resulting in a reduced p02 environment. As a further complication, a secondary immune response often occurs where fibrotic overgrowth foul the synthetic material to such an extent that the transport rate is severely reduced. We hypothesize that some of these oxygen limitations might be overcome if the transplanted cells have an increased affinity for oxygen transport in low p02 environments. To do this, we propose to genetically alter the cells to express myoglobin. It is predicted that the myoglobin will facilitate oxygen transport in the cell in low oxygen environments. We believe the successful implementations of this technology will dramatically improve the potential for cell transplantation in a variety of applications associated with bioartificial organs and tissue engineering. This proposed research will determine the feasibility of this approach for improving oxygen transport in low p02 environments.