Oct./2007
(STRATEGIC PROPOSALS)
Stem Cell Homeostasis- Fundamental Research on Mechanism of Stem Cell Homeostasis to Acceleration of Research and Development for Regenerative Medicine-/CRDS-FY2007-SP-05
Executive Summary

In this strategic program, we propose the research plan to integratively understand dynamic mechanisms by stem cells including cancer stem cells and aging processes to progress the research and development of regenerative medicines.
“Stem Cell Homeostasis” promotes fundamental researches focusing on the biological mechanisms of stem cells to maintain the cellular hierarchy in human physical environment, and then develop the technology to control stem cell functions both in-vivo and –vitro for connecting basic biological findings to clinical trials. Concerning research materials, human somatic stem cells are prior to pluripotent stem cells in the views of tumorigenesis, although their pluripotency may offer tremendous seeds in the future.

It is widely expected that regenerative medicine built on cellular functions may treat incurable diseases with present medicine . In Japan, we have focused so far on the development of in vitro cellular control technology based on the elucidation of proliferation and differentiation mechanisms of stem cells particularly for the purpose of cell transplantation as regenerative medicine. Even that a growing need for the safety and efficacy of transplant cells themselves requires the technology development which predicts adverse effects by cell graft in vitro before transplantation, or optimizes the transplanted cells that can stand and function in the tissue. The above means that the understanding of the mechanisms of the homeostasis in tissue as well as the maintaining ones leads the efficient translations from basic lab research to clinical trials using cell therapy technologies. On the other hand, it is getting recognized that several intractable diseases needs novel regenerative medicine which is different approaches from the cell therapy methodology. For example, in case that the etiology is located in the niche of the patient body less effect will be expected by the cell therapy. In stead, it is better to recover the dysfunction in given tissue by chemical stimulation which may activate tissue stem cells and induce rejuvenescence. In order to realize such type of medicines with stem cell activation, we need to understand biological mechanisms to cause the aberration of niche to develop the medical technology to activate the stem cells without side effect.
Therefore, we propose a strategy to promote fundamental research on human somatic stem cells in order to accelerate the development of regenerative medicine. Especially, following two issues are to be progressed;

1. Researches related to the maintain a homeostasis of stem cells such like “epigenetics of stem cells” and “controlling stem cells based on functions of its niche”
2. Researches related to the mechanisms to breakdown the stem cell homeostasis including “risk assessment of tumor formation based on cancer stem cells” and “impact of internal environment on stem cell functions”

The approaches of “epigenetics of stem cells”, which contains the researches which formalizes stem cell condition as well as brings biological markers of somatic stem cells may deliver fundamental findings to other research topics. By calling for proposal of this research area, it may take 5 years to connect basic studies which develop the controlling technology of stem cells to clinical trials. On should consider that the human embryonic stem cells contain more risky factors compared to tissue stem cells. It means that our proposal mainly focuses on the studies related to “epigenetics of stem cells” and “risk assessment of tumor formation based on cancer stem cells”.

By investment of “Stem Cell Homeostasis” program, we can develop technical seeds of future medicine to treat various disease and then accelerate the research and development of regenerative medicines. As a result, stem cell research in Japan would be progressed as integrative research areas in the views of human tissue formulation process and understanding the mechanisms of pathogenesis.