Peptide for inducing regeneration of tissue and use thereof
Inventors
Tamai, Katsuto • Yamazaki, Takehiko • Kanezaki, Tsutomu • Sakurai, Shigeru • NOGUCHI, Yukiko • Endo, Mayumi • Hamabuchi, Natsumi • Naito, Kana
Assignees
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Publication Number
US-10364276-B2
Publication Date
2019-07-30
Expiration Date
Abstract
(Objective) An objective of the present invention is to provide therapeutic agents that, in association with stimulation of PDGFRα-positive cells such as bone marrow mesenchymal stem cells, promote their mobilization into blood and accumulation in a damaged tissue, and induce tissue regeneration in a living body.(Means for solution) Multiple peptides were synthesized, and the migration-promoting activity of each peptide was evaluated. As a result, the present inventors successfully identified multiple peptides that have migration-promoting activity on a PDGFRα-positive bone marrow mesenchymal stem cell line (MSC-1). Further, the present inventors confirmed that the identified peptides also have migration-promoting activity on skin fibroblasts, which are PDGFRα-positive cells.
Core Innovation
The invention relates to HMGB1-derived peptides having cell migration-stimulating activity. The peptides are portions of an HMGB1 protein and are administered to stimulate migration of a cell, mobilize a cell from bone marrow to peripheral blood, and regenerate tissue in a subject.
The embodiments include a peptide, a cell secreting the peptide, or a vector into which DNA encoding the peptide is inserted. The peptides are derived from specific regions of HMGB1, including HMGB1 A-box, HMGB1 B-box, and the acidic tail, and the peptide consists of all or part of the amino acid sequence of positions 1 to 195 of SEQ ID NO:1.
Removing the C-terminal acidic tail corresponding to amino acids 186 to 215 can increase migration activity. The document also describes application to skin wound-healing models and reports in vivo effects including mobilization of PDGFRα+CD44+ cells into peripheral blood and reduced infarct size in a rodent stroke model.
Claims Coverage
The independent claim coverage centers on an HMGB1-derived peptide having cell migration-stimulating activity, with three alternatives for administration. The inventive features include the peptide composition and its administration, along with cells secreting the peptide or a vector encoding the peptide.
Administering an HMGB1-derived migration-stimulating peptide
Administering to the subject an effective amount of a substance comprising a peptide consisting of a portion of an HMGB1 protein of SEQ ID NO:1 and having cell migration-stimulating activity.
Administering cells secreting an HMGB1-derived migration-stimulating peptide
Administering to the subject an effective amount of a substance comprising a cell secreting the peptide that consists of a portion of an HMGB1 protein of SEQ ID NO:1 and having cell migration-stimulating activity.
Administering a vector encoding an HMGB1-derived migration-stimulating peptide
Administering to the subject an effective amount of a vector into which a DNA encoding the peptide is inserted, wherein the peptide has an activity of stimulating migration of a cell and consists of all or part of the amino acid sequence of positions 1 to 195 of SEQ ID NO:1.
Exclusion of HMGB1 acidic tail
The peptide excludes amino acids 186 to 215 of SEQ ID NO:1.
The inventive coverage centers on delivering an HMGB1-derived peptide fragment, or embodiments that produce it, with cell migration-stimulating activity. The peptide sequence is defined by all or part of amino acid positions 1 to 195 of SEQ ID NO:1, and the claims further include exclusion of amino acids 186 to 215.
Stated Advantages
Increased migration activity by removing the C-terminal acidic tail (amino acids 186 to 215).
Improved efficacy of shorter peptide core sequences.
Reduced production cost for shorter peptides.
Stimulating migration of a cell.
Mobilizing a cell from bone marrow to peripheral blood.
Regenerating a tissue in the body of a subject.
Documented Applications
Promoting migration of fibroblasts and bone-marrow mesenchymal stem cells using HMGB1-derived fragments and peptides.
Recruiting PDGFRα-positive and CD44-positive cells into peripheral blood in vivo.
Reducing infarct size in a rodent stroke model.
Skin wound-healing models, including necrosis and ulceration contexts.
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