Osaka University

Stemrim Inc.

Genomix Co., Ltd.

The University of Osaka

Takehiko Yamazaki

Katsuto Tamai

Yasufumi Kaneda

Takashi Shimbo

Takenao Chino

Mayumi Endo

Yoshiki Sawa

Shigeru Miyagawa

Kana Naito

Natsumi Hamabuchi

Yukiko Noguchi

Shigeru Sakurai

Tsutomu Kanezaki

Kotaro Saga

Wenhao Cui

Sokichi Kamata

Takashi Kido

Takasumi Goto

Eiji Sasaki

Takahiro Tsushima

The present inventors discovered that an HMGB1 fragment peptide having a specific amino acid sequence exhibits an effect of suppressing erythema, scaling (desquamation), and thickening (infiltration) of the skin in an animal model of psoriasis. Based on these findings, pharmaceutical compositions for the prevention and/or treatment of psoriasis, which comprise the HMGB1 fragment peptide having the specific amino acid sequence are provided.

Therapeutic agent for psoriasis

The inventors discovered that ectodermal mesenchymal stem cells circulating in peripheral blood that are induced by necrotic tissue damage contribute to the regeneration of damaged tissue. On the basis of this discovery, provided are ectodermal mesenchymal stem cells, a method for producing the same, and a screening method for a substance having pluripotent stem cell inductive activity, the screening method using cells induced by necrotic tissue damage in peripheral blood as an index.

Ectodermal mesenchymal stem cells and method for producing same

The present inventors identified many nuclear proteins contained in the extract of skin tissue by mass spectrometry, randomly selected multiple partial amino acid sequences of the nuclear proteins, chemically synthesized peptides consisting of the partial amino acid sequences, and examined their activity of mobilizing mesenchymal stem cells. As a result, it was found that these multiple peptides show the activity of mobilizing mesenchymal stem cells into peripheral blood, even though their amino acid sequences are completely different from each other. The inventors also found that fragment peptides of the nuclear proteins have therapeutic effects on diseases characterized by inflammation and abnormalities of the immune system (e.g., inflammatory bowel disease and psoriasis). Based on these findings, a new regenerative medicine technology that can overcome the problems of cell transplantation therapy is provided.

Disease treatment drug based on mesenchymal-stem-cell mobilization

The present inventors have found that HMGB1 fragment peptides having a particular amino acid sequence exhibit the effects of improvement of cardiac function, inhibition of cardiomyocyte hypertrophy, inhibition of myocardial fibrosis, and promotion of angiogenesis in an animal model of dilated cardiomyopathy, that the particular HMGB1 fragment peptides also exhibit the effects of improvement of cardiac function, inhibition of cardiomegaly, inhibition of cardiomyocyte hypertrophy, inhibition of myocardial fibrosis, and promotion of angiogenesis in an animal model of ischemic cardiomyopathy caused by old myocardial infarction, and that the particular HMGB1 fragment peptides exhibit the effects of inhibition of cardiomyocyte hypertrophy and inhibition of myocardial fibrosis in an animal model of hypertensive cardiomyopathy. Based on these findings, pharmaceutical compositions are provided for the prevention and/or treatment of cardiomyopathy and old myocardial infarction and chronic heart failure resulting therefrom, which comprise an HMGB1 fragment peptide having a particular amino acid sequence.

Therapeutic agent for cardiomyopathy, old myocardial infarction and chronic heart failure

The present inventors discovered that an HMGB1 fragment peptide having a specific amino acid sequence exhibits an effect of suppressing weight loss and an effect of suppressing shortening of the large intestine and mucosal damage in an animal model of inflammatory bowel diseases. Based on these findings, pharmaceutical compositions for the prevention and/or treatment of inflammatory bowel diseases, which comprise the HMGB1 fragment peptide having the specific amino acid sequence are provided.

Therapeutic agent for inflammatory bowel disease

Biologically low invasive vessels are filled with biological factors that have the activity of mobilizing specific functional cells in the body. The vessels are indwelled in the body. After specific functional cells are mobilized into the vessels, the vessels are removed from the body to collect functional cell populations mobilized to the vessels. Alternatively, the cells are directly collected from the vessels indwelled in the body.

Method for collecting functional cells in vivo with high efficiency

It was revealed that the intravenous administration of HMGB-1 and S100A8 promoted the healing of skin ulcer by recruiting bone marrow-derived cells to the site of skin ulcer. Furthermore, when HMGB-1 was intravenously administered to cerebral infarction model mice after creation of cerebral infarction, bone marrow-derived cells expressing nerve cell markers were detected in their brain. A marked cerebral infarct-reducing effect was observed in mice intravenously administered with HMGB-1 as compared to the control. The post-cerebral infarction survival rate was increased in the intravenous HMGB-1 administration group. The involvement of bone marrow pluripotent stem cells in the process of bone fracture healing was assessed using mice, and the result demonstrated that bone marrow-derived cells distant from the damaged site migrated to the bone fracture site to repair the damaged tissue.

Agents for promoting tissue regeneration by recruiting bone marrow mesenchymal stem cells and/or pluripotent stem cells into blood

(Objective) An objective of the present invention is to provide therapeutic agents that, in association with stimulation of PDGFR&#x3b1;-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 PDGFR&#x3b1;-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 PDGFR&#x3b1;-positive cells.

Peptide for inducing regeneration of tissue and use thereof

Fragment peptides having a proper length, which consists of a portion of the HMGB1 protein were synthesized, and the peptides were confirmed to show therapeutic effects on injury of the spinal cord.

Method for treating spinal cord injury using HMGB1 fragment

A fragment peptide having a proper length composed of a part of an HMGB1 protein was synthesized and the peptide was confirmed to exhibit therapeutic effects on myocardial infarction.

Method for treating cardiac infarction using HMGB1 fragment

The present invention for the first time demonstrated that:

Growing community of inventors

Osaka, Japan

Takehiko Yamazaki