Stem Cell Therapy Science
- Development of world-first, Osaka-original regeneration-inducing medicine
- What is a role of mesenchymal blood cells in vivo?
- How tissues maintain their stem cells in vivo?
- How injury-derived signals activate tissue stem cells?
Crosstalk between injury signals and tissue stem cells for maintaining tissue homeostasis
The structure and function of each tissue in the living body are maintained by its tissue stem cells. These stem cells respond to tissue injury, but if their number or function is insufficient, fibrotic scar tissue forms and inferior repair occurs. Regenerative medicine aims to manipulate tissue stem cells so as to maximize the regeneration response to an injured site. One example is stem cell transplantation, which is currently energetically advocated, suggesting the possibility of inducing regeneration.
As an example of severe tissue injury, we are studying epidermolysis bullosa (EB), a genetic skin disease. We have shown that necrotic epidermal cells in EB skin release the protein HMGB1, which causes bone marrow-derived mesenchymal stem cells to accumulate around the necrotic tissue and that this accumulation could promote regeneration. Photo: Bone marrow-derived mesenchymal stem cells promote skin regeneration in EB mice. Cells showing green fluorescence indicate accumulation of the bone marrow-derived mesenchymal stem cells in the regenerating EB mouse skin.
In normal tissues, HMGB1 functions as a chaperone protein that regulates gene expression by controlling the chromatin structure through DNA binding. Cell necrosis causes its release to the extracellular environment, which stimulates the innate immune system to accumulate neutrophils and macrophages in the necrotic tissue. Our research has demonstrated the additional important role of HMGB1 on maintaining tissue homeostasis after the necrotic injury.
Based on the above, we are investigating the molecular mechanism through which HMGB1 stimulates mesenchymal stem cells and other tissue stem cells. Since mesenchymal stem cells have been shown to have a regeneration-inducing potential for a number of diseases including cerebral infarctions, myocardial infarctions and GVHD (graft versus host disease), we are searching for HMGB1 peptides that mediate this potential by increasing mesenchymal blood cells.