title: Cinnamtannin B-1 Promotes Migration of Mesenchymal Stem Cells and Accelerates Wound Healing in Mice.
abstract: Substances that enhance the migration of mesenchymal stem cells to damaged sites have the potential to improve the effectiveness of tissue repair. We previously found that ethanol extracts of Mallotus philippinensis bark promoted migration of mesenchymal stem cells and improved wound healing in a mouse model. We also demonstrated that bark extracts contain cinnamtannin B-1, a flavonoid with in vitro migratory activity against mesenchymal stem cells. However, the in vivo effects of cinnamtannin B-1 on the migration of mesenchymal stem cells and underlying mechanism of this action remain unknown. Therefore, we examined the effects of cinnamtannin B-1 on in vivo migration of mesenchymal stem cells and wound healing in mice. In addition, we characterized cinnamtannin B-1-induced migration of mesenchymal stem cells pharmacologically and structurally. The mobilization of endogenous mesenchymal stem cells into the blood circulation was enhanced in cinnamtannin B-1-treated mice as shown by flow cytometric analysis of peripheral blood cells. Whole animal imaging analysis using luciferase-expressing mesenchymal stem cells as a tracer revealed that cinnamtannin B-1 increased the homing of mesenchymal stem cells to wounds and accelerated healing in a diabetic mouse model. Additionally, the cinnamtannin B-1-induced migration of mesenchymal stem cells was pharmacologically susceptible to inhibitors of phosphatidylinositol 3-kinase, phospholipase C, lipoxygenase, and purines. Furthermore, biflavonoids with similar structural features to cinnamtannin B-1 also augmented the migration of mesenchymal stem cells by similar pharmacological mechanisms. These results demonstrate that cinnamtannin B-1 promoted mesenchymal stem cell migration in vivo and improved wound healing in mice. Furthermore, the results reveal that cinnamtannin B-1-induced migration of mesenchymal stem cells may be mediated by specific signaling pathways, and the flavonoid skeleton may be relevant to its effects on mesenchymal stem cell migration.
authors.affiliation: Skin Regeneration, PIAS Collaborative Research, UIC, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Fujita
authors.affiliation: Skin Regeneration, PIAS Collaborative Research, UIC, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Kuge
authors.affiliation: Skin Regeneration, PIAS Collaborative Research, UIC, Osaka University, Suita, Osaka, 565-0871, Japan.|Research and Development Division, PIAS Corporation, Kobe, Hyogo, 651-2241, Japan.
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Ozawa
authors.affiliation: Skin Regeneration, PIAS Collaborative Research, UIC, Osaka University, Suita, Osaka, 565-0871, Japan.|Research and Development Division, PIAS Corporation, Kobe, Hyogo, 651-2241, Japan.
authors.forename: Shunya
authors.initials: S
authors.lastname: Sahara
authors.affiliation: Skin Regeneration, PIAS Collaborative Research, UIC, Osaka University, Suita, Osaka, 565-0871, Japan.|Research and Development Division, PIAS Corporation, Kobe, Hyogo, 651-2241, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Zaiki
authors.affiliation: Skin Regeneration, PIAS Collaborative Research, UIC, Osaka University, Suita, Osaka, 565-0871, Japan.|Research and Development Division, PIAS Corporation, Kobe, Hyogo, 651-2241, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakaoji
authors.affiliation: Research and Development Division, PIAS Corporation, Kobe, Hyogo, 651-2241, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hamada
authors.affiliation: Organic Chemistry Department, Kobe Pharmaceutical University, Kobe, Hyogo, 658-8558, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Takenaka
authors.affiliation: Organic Chemistry Department, Kobe Pharmaceutical University, Kobe, Hyogo, 658-8558, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Tanahashi
authors.affiliation: Division of Stem Cell Therapy Science, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Katsuto
authors.initials: K
authors.lastname: Tamai
authors.affiliation: Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kaneda
authors.affiliation: Skin Regeneration, PIAS Collaborative Research, UIC, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Maeda
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D059808:Polyphenols / Q000494:pharmacology; D044945:Proanthocyanidins / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D005419:Flavonoids; D059808:Polyphenols; D044945:Proanthocyanidins; C517872:cinnamtannin B-1