Fucoidan protects mesenchymal stem cells against oxidative stress and enhances vascular regeneration in a murine hindlimb ischemia model.

Abstract

BACKGROUND:

Mesenchymal stem cells (MSCs) have the potential to differentiate into multiple cell lineages. Given this potential for tissue regeneration, MSC-based therapeutic applications have been considered in recent years. However, ischemia-induced apoptosis has been reported to be one of the main causes of MSC death following transplantation. The primary objective of this study was to determine whether a natural antioxidant, fucoidan, could protect MSCs from ischemia-induced apoptosis in vitro and in vivo. Furthermore, we investigated the mechanism of action of fucoidan's anti-ischemic effect in MSCs.

METHODS AND RESULT:

Pre-treatment with fucoidan (10 μg/mL) suppressed the increase in H2O2-induced reactive oxygen species (ROS) levels and drastically reduced apoptotic cell death in MSCs. Fucoidan inhibited the activation of the pro-apoptotic proteins p38-mitogen-activated protein kinase (MAPK), Jun N-terminal kinase (JNK), and caspase-3, and augmented the expression of the anti-apoptosis protein cellular inhibitor of apoptosis (cIAP). Moreover, fucoidan significantly increased manganese superoxide dismutase (MnSOD) expression and decreased cellular ROS levels via the Akt pathway, resulting in enhanced cell survival. In a murine hindlimb ischemia model, transplanted fucoidan-treated MSCs showed significantly enhanced cell survival and proliferation in ischemic tissues. Functional recovery and limb salvage also remarkably improved in mice injected with fucoidan-stimulated MSCs compared with mice injected with non-stimulated MSCs.

CONCLUSION:

Taken together, these results show that fucoidan protects MSCs from ischemia-induced cell death by modulation of apoptosis-associated proteins and cellular ROS levels through regulation of the MnSOD and Akt pathways, suggesting that fucoidan could be powerful therapeutic adjuvant for MSC-based therapy in ischemic diseases.

• Authors: Yong-Seok Han, Jun Hee Lee, Jin Sup Jung, Hyunjin Noh, Moo Jun Baek, Jung Min Ryu, Yeo Min Yoon, Ho Jae Han, Sang Hun Lee
• Journal: International journal of cardiology (Int J Cardiol) Vol. 198 Pg. 187-95 (Nov 01 2015) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 26163916 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Polysaccharides
• fucoidan

Topics

• Animals
• Cell Survival (drug effects, physiology)
• Dose-Response Relationship, Drug
• Hindlimb (blood supply)
• Humans
• Ischemia (drug therapy, pathology)
• Mesenchymal Stem Cell Transplantation (methods)
• Mesenchymal Stem Cells (drug effects, physiology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neovascularization, Physiologic (drug effects, physiology)
• Oxidative Stress (drug effects, physiology)
• Polysaccharides (pharmacology, therapeutic use)