Cinnamtannin B-1 Promotes Migration of Mesenchymal Stem Cells and Accelerates Wound Healing in Mice.

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 mo...

Full description

Saved in:
Bibliographic Details
Main Authors: Kosuke Fujita, Katsunori Kuge, Noriyasu Ozawa, Shunya Sahara, Kaori Zaiki, Koichi Nakaoji, Kazuhiko Hamada, Yukiko Takenaka, Takao Tanahashi, Katsuto Tamai, Yasufumi Kaneda, Akito Maeda
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0144166&type=printable
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850189347952787456
author Kosuke Fujita
Katsunori Kuge
Noriyasu Ozawa
Shunya Sahara
Kaori Zaiki
Koichi Nakaoji
Kazuhiko Hamada
Yukiko Takenaka
Takao Tanahashi
Katsuto Tamai
Yasufumi Kaneda
Akito Maeda
author_facet Kosuke Fujita
Katsunori Kuge
Noriyasu Ozawa
Shunya Sahara
Kaori Zaiki
Koichi Nakaoji
Kazuhiko Hamada
Yukiko Takenaka
Takao Tanahashi
Katsuto Tamai
Yasufumi Kaneda
Akito Maeda
author_sort Kosuke Fujita
collection DOAJ
description 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.
format Article
id doaj-art-90ff1f70103a47cb83b387a4fa1ee09b
institution OA Journals
issn 1932-6203
language English
publishDate 2015-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-90ff1f70103a47cb83b387a4fa1ee09b2025-08-20T02:15:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014416610.1371/journal.pone.0144166Cinnamtannin B-1 Promotes Migration of Mesenchymal Stem Cells and Accelerates Wound Healing in Mice.Kosuke FujitaKatsunori KugeNoriyasu OzawaShunya SaharaKaori ZaikiKoichi NakaojiKazuhiko HamadaYukiko TakenakaTakao TanahashiKatsuto TamaiYasufumi KanedaAkito MaedaSubstances 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0144166&type=printable
spellingShingle Kosuke Fujita
Katsunori Kuge
Noriyasu Ozawa
Shunya Sahara
Kaori Zaiki
Koichi Nakaoji
Kazuhiko Hamada
Yukiko Takenaka
Takao Tanahashi
Katsuto Tamai
Yasufumi Kaneda
Akito Maeda
Cinnamtannin B-1 Promotes Migration of Mesenchymal Stem Cells and Accelerates Wound Healing in Mice.
PLoS ONE
title Cinnamtannin B-1 Promotes Migration of Mesenchymal Stem Cells and Accelerates Wound Healing in Mice.
title_full Cinnamtannin B-1 Promotes Migration of Mesenchymal Stem Cells and Accelerates Wound Healing in Mice.
title_fullStr Cinnamtannin B-1 Promotes Migration of Mesenchymal Stem Cells and Accelerates Wound Healing in Mice.
title_full_unstemmed Cinnamtannin B-1 Promotes Migration of Mesenchymal Stem Cells and Accelerates Wound Healing in Mice.
title_short Cinnamtannin B-1 Promotes Migration of Mesenchymal Stem Cells and Accelerates Wound Healing in Mice.
title_sort cinnamtannin b 1 promotes migration of mesenchymal stem cells and accelerates wound healing in mice
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0144166&type=printable
work_keys_str_mv AT kosukefujita cinnamtanninb1promotesmigrationofmesenchymalstemcellsandaccelerateswoundhealinginmice
AT katsunorikuge cinnamtanninb1promotesmigrationofmesenchymalstemcellsandaccelerateswoundhealinginmice
AT noriyasuozawa cinnamtanninb1promotesmigrationofmesenchymalstemcellsandaccelerateswoundhealinginmice
AT shunyasahara cinnamtanninb1promotesmigrationofmesenchymalstemcellsandaccelerateswoundhealinginmice
AT kaorizaiki cinnamtanninb1promotesmigrationofmesenchymalstemcellsandaccelerateswoundhealinginmice
AT koichinakaoji cinnamtanninb1promotesmigrationofmesenchymalstemcellsandaccelerateswoundhealinginmice
AT kazuhikohamada cinnamtanninb1promotesmigrationofmesenchymalstemcellsandaccelerateswoundhealinginmice
AT yukikotakenaka cinnamtanninb1promotesmigrationofmesenchymalstemcellsandaccelerateswoundhealinginmice
AT takaotanahashi cinnamtanninb1promotesmigrationofmesenchymalstemcellsandaccelerateswoundhealinginmice
AT katsutotamai cinnamtanninb1promotesmigrationofmesenchymalstemcellsandaccelerateswoundhealinginmice
AT yasufumikaneda cinnamtanninb1promotesmigrationofmesenchymalstemcellsandaccelerateswoundhealinginmice
AT akitomaeda cinnamtanninb1promotesmigrationofmesenchymalstemcellsandaccelerateswoundhealinginmice