T003E

Angiogenic Peptide for Reconstruction Medicine
Research tools & Theranostics•Applications of immobilized cyclic-peptide Libraries (Diagnoses, Theranostics)•Bioconjugates: Peptide-Vehicle （DDS/Therapeutics)

Angiogenic Peptide for Reconstruction Medicine•

Biomimetic, biodegradable and biocompatible materials for hard tissue reconstruction →highlighted for improving the QOL•

Further improvements → Functional peptides are immobilized directly on gelatin (collagen) →Replacement of hard tissues. Nokihara, K. et al, Peptide Science 2000, 373, 2001.

•Bioconjugates: transformed rat lung endothelial cells (Adhesion Assay Wound Assay) → directed
towards cell adhesion and angiogenesis of endothelial cells. The Raito of Peptide vs. Carrier
Protein had been optimized.

•In addition to the adhesion activity, a significant angiogenic activity exhibited peptide, designated
AGP, angiogenic peptide has been discovered (USA EU & Japan-Patents). BBRC, 310,153-7, 2003.
Licensing, Material supply including library → Practical application (Preclinical to Clinical Phases)

Assay using a discangiogenesis-system

ControlMorphological evidence for Tube formationAGP

Implantation of the chamber indorsum of mice

X 15000

X 7000tight junction

Microvilli
Heart regenerative medicine
γSkM=Skeletal myoblasts
SV=AGP peptide
Haematoxylin- and eosin-stained sectionof the left ventricle:(a) control; (b) WT-rSkM; and (c) SV-rSkM (×10 magnification, scale bars
represent 1000 mm).

Uchinaka A., et al., Cardiovasc. Res. 2013

HiPep Laboratories, Nakatsukasa-cho 486-46, Kamigyo-ku, Kyoto, 602-8158, Japan
Tel +81-75-813-2101 E-mail: PepTenChip@hipep.jp URL: http://www.hipep.jp/1

T003EAngiogenic Peptide for Reconstruction Medicine
1. Three dimensional cell culture was prepared to check the morphogenesis. Beside adhesion, we found tubular formation
which was more pronounced for the AGP than VEGF
2. Normally monolayer-cultured endothelial cells do not show these cell differentiations.
3. Angiogenic effects were present in vitro. We have also carried out in vivo assays using the disc-angiogenesis-systemwith mice.
4. The peptide induced angiogenic effects were quantified according to the degree of newly formed blood vessels. We
found that peptide AGP has a significant angiogenic activity.
5. The adhesion activity of AGP has already been reported but not its angiogenic properties.
6. No new blood vessels were observed in the control, VEGF induced neovalscularization moderately and the present
AGP showed remarkable angiogenesis.
7. The results indicated that the residues located in the middle section of the peptide, in particular Tyr at position 4, areimportant while both the N- and C-termini are not crucial. Therefore immobilization at both ends of the peptide has noinfluence on its desired actions.
8. Novel biomimetic, biodegradable and biocompartible materials, which can be used for reconstruction of defective
tissues, are in great demand.
9. Hence, both adhesion and angiogenesis are key factors for achieving the normal functioning of implanted artificialorgans and for rapid healing.
ContexPaper

Angiogenic activity

Biochem. Biophys. Res. Commun. 310, 153-157, 2003

Neovascularization in artificial bonemarrow scaffold biomaterials

Dent. Mater. J. 26, 487-492, 2007

Enhanced bone regeneration

Biomaterials 30, 4676-4686, 2009

Tissue engineering biomaterialsDent Mater J. 29, 1-8, 2010
J. Mater. Sci. Mater. Med. 23, 2761-2772
PLoS One 7, e41163,2012

Tissue regeneration

Bioconjug. Chem. 23, 2042-2050, 2012

Cardiac regeneration therapy

Cardiovasc Res. 99, 102-110, 2013
Mol Cell Biochem. 408, 191-203, 2015
Interact. Cardiovasc. Thorac. Surg. 21, 506-514, 2015

HUVEC adhesion

Biomed. Mater. Res. A. 104, 1425-1436, 2016

Related pulications
1.
Uchinaka A, Kawaguchi N, Hamada Y, Mori S, Miyagawa S, Saito A, Sawa Y, Matsuura N. Cardiovasc. Res., 99, 102-110,2013.Transplantation of myoblast sheets that secrete the novel peptide SVVYGLR improves cardiac function in failinghearts2.
Egusa, H., Kaneda, Y., Akashi, Y., Hamada, Y., Matsumoto, T., Saeki, M., Thakor, D. K., Tabata, Y., Matsuura, N., Yatani,
H. Biomaterials, 30, 4676-4686, 2009. Enhanced bone regeneration via multimodal actions of synthetic peptide SVVYGLR
on osteoprogenitors and osteoclasts
3.
Hamada, Y., Egusa, H., Kaneda, Y., Hirata, I., Kawaguchi, N., Hirao, T., Matsumoto, T., Yao, M., Daito, K., Suzuki, M.,Yatani, H., Daito, M., Okazaki, M., Matsuura, N. Dent. Mater. J., 26, 487-492, 2007.Synthetic osteopontin-derived peptide
SVVYGLR can induce neovascularization in artificial bone marrow scaffold biomaterials
4.
Hamada, Y., Nokihara, K., Okazaki, M., Fujitani, W., Matsumoto, T., Matsuo, M., Umakoshi, Y., Takahashi, J., Matsuura, N.
Biochem. Biophys. Res.Commun., 310, 153-157, 2003. Angiogenic activity of osteopontin-derived peptide SVVYGLR
5.
Okazaki, M., Yamazaki, Y., Yoshida, Y., Shimadzu, A., Nokihara, K., Hamada, Y., Takahashi, J., and Matsuura, N. Dentistryin Japan, 37, 95-100, 2001.A New Concept of CO3 apatite Collagen Composites with Adhesion Motif as Biomaterials
6.
Nokihara, K., Hamada, Y., Takahashi, J., Okazaki, M., and Matsuura, N. Peptide Science 2001, ed. Aoyagi, H., TheJapanese Peptide Society, 359-362, 2002.Development of Biomedical Materials Carrying Immobilized Functional Peptides
and Discovery of an Angiogenic Peptide
7.
Nokihara, K., Blahunka, A., Yamazaki, Y., Yoshida, Y., and Okazaki, M. Peptide Science 2000, ed. Shioiri, T.,The JapanesePeptide Society, Osaka, 373-376, 2001.Development of Biomimetic Materials: Novel Composite Material Carrying
Immobilized Functional Peptides

HiPep Laboratories, Nakatsukasa-cho 486-46, Kamigyo-ku, Kyoto, 602-8158, Japan
Tel +81-75-813-2101 E-mail: PepTenChip@hipep.jp URL: http://www.hipep.jp/2