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

Han, Yong‐Seok; Lee, Jun Hee; Jung, Jin Sup; Noh, Hyunjin; Baek, Moo Jun; Ryu, Jung Min; Yoon, Yeup; Han, Ho Jae; Lee, Sang Hun

doi:10.1016/j.ijcard.2015.06.070

Cited by 49 publications

(43 citation statements)

References 26 publications

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“…In particular, downregulation of PrP C increases phosphorylation of extracellular signal-regulated kinases 1/2 and reduces the activation of Akt, resulting in an increase in caspase-3 activity36. In addition, enhancement of Akt-mediated MnSOD expression promotes protection of MSCs against oxidative stress in vitro and in vivo 37. Akt is a central cell signaling molecule downstream to cytokines, growth factors, and several stimulations38.…”

Section: Discussionmentioning

confidence: 99%

Tauroursodeoxycholic acid reduces ER stress by regulating of Akt-dependent cellular prion protein

Yoon

Lee

Yun

et al. 2016

Sci Rep

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Although mesenchymal stem cells (MSCs) are a promising cell source for regenerative medicine, ischemia-induced endoplasmic reticulum (ER) stress induces low MSC engraftment and limits their therapeutic efficacy. To overcome this, we investigated the protective effect of tauroursodeoxycholic acid (TUDCA), a bile acid, on ER stress in MSCs in vitro and in vivo. In ER stress conditions, TUDCA treatment of MSCs reduced the activation of ER stress-associated proteins, including GRP78, PERK, eIF2α, ATF4, IRE1α, JNK, p38, and CHOP. In particular, TUDCA inhibited the dissociation between GRP78 and PERK, resulting in reduced ER stress-mediated cell death. Next, to explore the ER stress protective mechanism induced by TUDCA treatment, TUDCA-mediated cellular prion protein (PrPC) activation was assessed. TUDCA treatment increased PrPC expression, which was regulated by Akt phosphorylation. Manganese-dependent superoxide dismutase (MnSOD) expression also increased significantly in response to signaling through the TUDCA-Akt axis. In a murine hindlimb ischemia model, TUDCA-treated MSC transplantation augmented the blood perfusion ratio, vessel formation, and transplanted cell survival more than untreated MSC transplantation did. Augmented functional recovery following MSC transplantation was blocked by PrPC downregulation. This study is the first to demonstrate that TUDCA protects MSCs against ER stress via Akt-dependent PrPC and Akt-MnSOD pathway.

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Section: Discussionmentioning

confidence: 99%

Tauroursodeoxycholic acid reduces ER stress by regulating of Akt-dependent cellular prion protein

Yoon

Lee

Yun

et al. 2016

Sci Rep

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“…Another compound, tricyclodecan‐9‐yl‐xanthogenate markedly increases the number of MSCs differentiating into neurons by increasing ROS levels and expression of antioxidative enzymes, but not by enhancing different SOD activities . Two medicines widely used clinically, fucoidan and carvedilol, protect in vitro MSCs from H 2 O 2 ‐induced injury via inhibition of p38‐MAPK, JNK, caspase 3 and AKT as well as ROS‐related pathways . Nicorandil attenuates Hy/SD‐induced apoptosis by reducing ROS generation, maintaining the stability of matrix metalloproteinases and decreasing the release of apoptosis‐related molecules .…”

Section: Strategies To Control Ros Levels For Msc Fates In Vitro and mentioning

confidence: 99%

Regulation of the mitochondrial reactive oxygen species: Strategies to control mesenchymal stem cell fates ex vivo and in vivo

Zhao

Peng

et al. 2018

J Cellular Molecular Medi

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Mesenchymal stem cells (MSCs) are broadly used in cell‐based regenerative medicine because of their self‐renewal and multilineage potencies in vitro and in vivo. To ensure sufficient amounts of MSCs for therapeutic purposes, cells are generally cultured in vitro for long‐term expansion or specific terminal differentiation until cell transplantation. Although physiologically up‐regulated reactive oxygen species (ROS) production is essential for maintenance of stem cell activities, abnormally high levels of ROS can harm MSCs both in vitro and in vivo. Overall, additional elucidation of the mechanisms by which physiological and pathological ROS are generated is necessary to better direct MSC fates and improve their therapeutic effects by controlling external ROS levels. In this review, we focus on the currently revealed ROS generation mechanisms and the regulatory routes for controlling their rates of proliferation, survival, senescence, apoptosis, and differentiation. A promising strategy in future regenerative medicine involves regulating ROS generation via various means to augment the therapeutic efficacy of MSCs, thus improving the prognosis of patients with terminal diseases.

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“…The dose‐depend effect on proliferation was also observed in human MSCs treated with fucoidan, extracted from brown alga Laminaria japonica (Kim et al , ) have shown the ability of fucoidan to enhance proliferation of human MSCs in dose‐depend manner after 2 days of culture at concentrations of 0.1–10 μg/mL. Enhanced proliferative activity of fucoidan‐treated MSCs, mediated by activation of Akt signalling pathway, was described in a murine hind limb ischemia model (Han et al , ; Lee et al , , b). At the same time, various studies revealed anti‐proliferative properties of fucoidan in tumour cell lines (Fukahori et al , ; Senthilkumar et al , ).…”

Section: Plant‐derived Bioactive Compoundsmentioning

confidence: 86%

The effects of chosen plant extracts and compounds on mesenchymal stem cells—a bridge between molecular nutrition and regenerative medicine‐ concise review

Kornicka

Kocherova

Marycz

2017

Phytotherapy Research

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Mesenchymal stem cells (MSC) stand as a promising tool in regenerative medicine because of their high therapeutic potential in treatment of degenerative, metabolic and other types of diseases. The cellular therapies involving MSCs include their isolation mainly from the bone marrow, adipose tissue or umbilical cord and in vitro expansion for further autologous or allogeneic transplantation. Recent studies revealed, that bioactive compounds, naturally occurring in seaweeds, herbs, fruits and vegetables, possess the ability to modulate self-renewal and differentiation potential of adult stem cells, targeting a broad range of intracellular signal transduction pathways. Number of ongoing trials aim to find a herbal extract that may become less toxic and affordable natural therapeutic. Mesenchymal stem cells are treated with crude extracts or individual compounds to investigate its effects and mechanism on stem cells proliferation and differentiation. Deeply investigated, herbal extract which increases tissue regeneration and promotes stem cell growth may be successfully applied in the field of biomaterials. Promoting the endogenous stem cell multipotency and their differentiation potential may additionally support the regenerative processes after MSCs transplantation. The review focuses on the beneficial effects of chosen plant derived substances on MSCs proliferative activity and their osteogenic differentiation potential. Copyright © 2017 John Wiley & Sons, Ltd.

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

Cited by 49 publications

References 26 publications

Tauroursodeoxycholic acid reduces ER stress by regulating of Akt-dependent cellular prion protein

Tauroursodeoxycholic acid reduces ER stress by regulating of Akt-dependent cellular prion protein

Regulation of the mitochondrial reactive oxygen species: Strategies to control mesenchymal stem cell fates ex vivo and in vivo

The effects of chosen plant extracts and compounds on mesenchymal stem cells—a bridge between molecular nutrition and regenerative medicine‐ concise review

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