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Int J Cardiol. 2015 Nov 1;198:187-95. doi: 10.1016/j.ijcard.2015.06.070. Epub 2015 Jun 27.

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

Author information

1
Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea.
2
Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 626-870, Republic of Korea.
3
Medical Research Center for Ischemic Tissue Engineering, Pusan National University, Yangsan, Gyeongnam, Republic of Korea; Department of Physiology, School of Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea.
4
Department of Internal Medicine, Soonchunhyang University, Seoul, Republic of Korea; Hyonam Kidney Laboratory, Soonchunhyang University, Seoul, Republic of Korea.
5
Department of Surgery, School of Medicine, Soonchunhyang University, Cheonan 330-930, Republic of Korea.
6
Department of Veterinary Physiology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 151-741, Republic of Korea; BK21 PLUS Creative Veterinary Research Center, Seoul National University, Seoul 151-741, Republic of Korea.
7
Department of Veterinary Physiology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 151-741, Republic of Korea; BK21 PLUS Creative Veterinary Research Center, Seoul National University, Seoul 151-741, Republic of Korea. Electronic address: hjhan@snu.ac.kr.
8
Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea; Department of Biochemistry, Soonchunhyang University College of Medicine, Cheonan 330-930, Republic of Korea. Electronic address: ykckss1114@nate.com.

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.

KEYWORDS:

Fucoidan; MSCs; MnSOD; Survival; Vascular repair

PMID:
26163916
DOI:
10.1016/j.ijcard.2015.06.070
[Indexed for MEDLINE]

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