hESC-Derivates Suppress Host Inflammation
The immune system is vital to protect the body against foreign invaders, such as viruses and bacteria. However, the protection brought about by the immune system can also prevent acceptance of transplanted tissues or organs. The rejection of transplanted tissues or organs by the host can typically be prevented by use of drugs called immunosuppressants. Immunosuppressants can dampen the immune response to foreign tissues and organs and allow for the tissue or organ to engraft to the host and carry out its function; without immunosuppression the transplant will not engraft. On this basis, it is also expected that stem cell-based transplants will also require immunosuppression for engraftment. Although use of immunosuppression can allow a transplant to engraft, it also weakens the immune defense against disease-causing foreign invaders. Thus, development of other mechanisms to prevent rejection of stem cell-based therapeutics is warranted.
Importantly, the lack of an immune response in a pregnant mother against the embryo or fetus that carries proteins foreign to her body suggests that the embryo or fetus has an innate means to suppress the immune system. If this ability to avoid immune rejection is innate to the embryo, then it may also be innate to the cells that make up the embryo. Indeed, research suggests that embryonic stem cells do not induce an immune response and can actually dampen an active immune response. Based on these observations, our laboratory and others examined the immune response to human embryonic stem cells differentiated in a manner compliant to FDA guidelines into a cell type with the potential to treat neurological diseases and traumas. The immune response to these differentiated cells was similar to undifferentiated human embryonic stem cells. This finding suggests that certain cells derived from embryonic stem cells might possess properties that can be innately tolerated by the immune system.
Although the differentiated cells were shown to be privileged from immune attack in isolated tests of immune reactions, there is no evidence that the cells will be tolerated by the immune system in animal models of trauma that have intact and ongoing immune reactions. Our proposed research project will therefore determine the ability of differentiated cells to interact or interfere with the immune system. This is possible because we have developed tools to differentiate reciprocal transplant and host responses. We also propose to examine if this effect is also present in another differentiated cell type derived from the same or a different line of human embryonic stem cells. The information gathered from this research will be important for determination of what interactions occur in both the transplant and the host during the initial period after transplantation and will help determine the immunosuppression needs for human embryonic cell transplants in this neural trauma.
This program will position California for international competitiveness in this emerging area of biotechnology, as our studies are critical to the clinical development of the two hESC-derivates used in our studies, one of which is within 12 months of being used in human clinical trials, and the second is within 12 months of being presented to the FDA for an IND. Thus, California will benefit from supporting the discovery of what will become the first and second human embryonic stem cell-based clinical trials in the world. This will result in California being a focus of the stem cell industry, including large pharmaceutical companies that will eventually participate in the latter stage stem cell clinical trials. Clinically relevant scientific advances lead to the development of biotechnology companies, creating jobs and taxation. Funding for this proposal will directly create new jobs. In these challenging economic times, we feel that any award should be spent in a manner which enhances the local and state economy, in essence returning direct value to the citizens of California. To this end, we have purposely selected suppliers of equipment and services that are located in the state of California. In addition, due to the booming medical device and biotechnology industries in California, we feel that all new hires can be obtained from within the state of California.