This strategic proposal aims to promote basic research that helps achieve preemptive medicine, by which clinical conditions are predicted with biomarkers and early intervention can be made; arguably one such strategy is to specifically focus on the self-repairing capacity of human cells that enables an innovative medical technology - "Preemptive Medicine using Self-Repairing"-.

Japan faces the issue of rapidly aging population combined with the diminishing number of children alongside the increasing the nation's total medical and care service expenditures. The latter came up with almost the same level of tax revenue of the nation. Therefore it is critical to reduce medical cost and to enhance the nation's healthy life-span whereby the aged can play a major productive role in the society. This cannot be achieved without medical technologies that help strike a right balance between therapeutic efficacy and appropriate medical cost.

In general, the more the state of diseases progresses, the less therapeutic efficacy can be expected, resulting in the increase in medical cost. In this view, in 2010, Center for Research and Development Strategy (CRDS), Japan Science and Technology Agency (JST), made a proposal on the new medical concept - preemptive medicine - with a view to predicting clinical conditions by using biomarkers and enabling early intervention both against the onset of diseases and the progression of the state of diseases.
The reality is that it is difficult to completely prevent all possible disease of every single individual. Therefore, a possible blue print of future medicine is that regenerative medicine provides alternative therapeutics for patients whose clinical conditions became severe at irreversible phases even after preemptive medicine is performed. However, our analyses on current technologies of regenerative medicine indicate that under the current technologies, only in limited cases such as epidermis, cornea, and cartilage, recipients' tissues can be replaced for functional substitution by cell therapy. Instead, what we currently have is technologies that can give indirect therapeutic effects to targeted patients' own cells (endogenous cells) by humoral factors secreted from transplanted cells. In this process, the more the state of diseases progresses, the less therapeutic efficacy will be expected due to the decrease of the capacity of self-repairing of cells. On the other hand, interventions of current regenerative medicine are made at very late stages of clinical conditions. Theoretically, if earlier interventions of regenerative medicine become possible, much higher therapeutic efficacy would be expected. However, it is technically difficult with current technologies. One of the reasons is the lack of understanding of functional mechanisms as well as safety and efficacy of cell therapy. Therefore, regenerative medicine (cell therapy) can be considered as a last resort of therapy when others are ineffective but not ideal to use it from early stages of clinical conditions. If those mechanisms are uncovered, early interventions would be possible and even cell therapy would be replaced with other therapeutic approaches such as chemicals and biological drugs. Such change will also be important in terms of reducing the expensive cost of cell therapy.
We hereby propose a strategy to promote basic research that helps enable preemptive self-repairing medicine" (Figure 1). Our aim is to achieve affordable and efficient therapies by shifting intervention points from later phases where current regenerative medicine is expected to play a major role, to early phases by preemptive self-repairing medicine.

Concept of "Preemptive Medicine using Self-Repairing
The term "preemptive" in this proposal indicates that prevention not only against the onset of diseases but also the progression of diseases. The term "self-repairing" indicates that the functional regeneration of tissues through the intervention on recipients' own cells. Therefore, the concept of the latter is not limited to that of stem cell research. In fact preemptive self-repairing is a new medical concept which helps predict clinical conditions by using biomarkers, and prevent the progression of diseases by utilizing the self-repairing capacity of recipients' own cells.

In order to achieve preemptive self-repairing, three major strategies of basic research are proposed.

Strategy 1:The establishment of interventional concepts
Strategy 2:The development of the diagnostic technologies for the early intervention
Strategy 3:The development of intervention technologies

In Strategy 1, molecular mechanisms of self-repairing in regenerative medicine or other clinical cases are uncovered and interventional concepts are developed. In Strategy 2, biomarkers and diagnostic systems are developed to identify right timing of interventions. In Strategy 3, therapeutic technologies, such as self-repairing accelerating/inhibiting substances and drug delivery systems, are developed by utilizing what is achieved by Strategy 1.

This proposal targets aging-associated diseases, including amongst others, cardiovascular, cranial nerve, kidney, endocrine, liver, digestive, pancreas, auto immune, and musculoskeletal diseases. We believe that achieving "preemptive self-repairing medicine" contributes to realize a healthy aging longevity.

The term "Preemptive Medicine" here indicates a medical concept, including not only prevention/delay against the onset of diseases but also the progression of diseases (red area). One the other hand, "Regenerative Medicine (narrow sense)" aims to achieve functional recovery of heavily damaged organs or tissues by transplanting cells, which are cultured outside of a recipient's body (blue area): The latter does not include the indirect therapeutic effects to targeted patients' own cells (endogenous cells) by humoral factors secreted from transplanted cell(self-repairing). In "current regenerative medicine", some enable "regenerative medicine in the strict sense" and others do "self-repairing" (circled in green). "Preemptive self-repairing medicine" is the approach to achieve higher therapeutic outcomes and reasonable cost by advancing the interventions of the "current regenerative medicine" to earlier clinical phases (circled in yellow).