HMGB1 Protein Mobilizing Stem Cells for Tissue Regeneration
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Solution Overview
Problem
Current regenerative medicines lack effective methods to mobilize bone marrow-derived stem cells to damaged tissues, particularly for skin and neurological tissue regeneration, where the mechanism for mobilizing these cells to lesion sites is unknown.
Innovation Solution
The use of HMGB1, HMGB2, and HMGB3 proteins or cells secreting these proteins, or vectors encoding them, to mobilize bone marrow-derived mesenchymal stem cells to damaged tissues by releasing them from necrotic tissue, facilitating their differentiation into various cell types for tissue regeneration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If regenerative medicines are developed to induce functional tissue regeneration, then tissue regeneration capability is improved, but the mechanism for mobilizing stem cells to lesion sites is unknown
Solution Approach 1:
The patent identifies HMGB1 as an intermediary substance that mediates between necrotic tissue and stem cells. HMGB1 is released from necrotic cells and acts as a signaling molecule to recruit bone marrow-derived stem cells to the lesion site, thereby filling the information gap about the mobilization mechanism while enabling tissue regeneration
2Productivity
If bone marrow-derived stem cells are mobilized to lesion sites, then tissue regeneration is promoted, but the method to mobilize these cells is not established
Solution Approach 1:
The patent employs a self-service mechanism where necrotic tissue automatically releases HMGB1 upon cell death, which then autonomously recruits stem cells to the lesion site. This eliminates the need for external intervention or complex mobilization protocols, as the damaged tissue itself provides the signaling function
Solution Approach 2:
The patent converts the harmful effect of necrosis (cell death and tissue damage) into a beneficial signaling event. Necrotic cells release HMGB1, which transforms the harmful necrotic process into a useful recruitment signal that attracts stem cells to the damaged area, thereby promoting regeneration
Data Source
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AI summary
The present inventors revealed the following for the first time in the world: 1) a large amount of bone marrow-derived cells are mobilized to grafted skin; 2) the mobilized bone marrow-derived cells are differentiated into any of dermal fibroblasts, adipocytes, muscle cells, vascular endothelial cells, and epidermal keratinocytes in the grafted skin, and the mobilized bone marrow-derived cells include bone marrow-derived mesenchymal stem cells; 3) the factors which mobilize bone marrow-derived mesenchymal stem cells from peripheral blood to the grafted skin are HMGB1, HMGB2, and HMGB3 released from the necrosed tissue of recipient skin; 4) purified HMGB1, HMGB2, and HMGB3 promote the migration of mesenchymal stem cells isolated and cultured from bone marrow; 5) activators containing HMGB1 which allows the migration of bone marrow mesenchymal stem cells can be conveniently purified from several organ extracts including skin, brain, and heart; 6) activators which allow the migration of bone marrow mesenchymal stem cells can be conveniently extracted from cultured cells; and 7) a heparin-column purified fraction of skin extract mobilizes a large amount of bone marrow-derived cells in case of brain injury.