title: Fucoidan improves bioactivity and vasculogenic potential of mesenchymal stem cells in murine hind limb ischemia associated with chronic kidney disease.
abstract: Chronic kidney disease (CKD) is a significant risk factor for cardiovascular and peripheral vascular disease. Although mesenchymal stem cell (MSC)-based therapy is a promising strategy for treatment of ischemic diseases associated with CKD, the associated pathophysiological conditions lead to low survival and proliferation of transplanted MSCs. To address these limitations, we investigated the effects of fucoidan, a sulfated polysaccharide, on the bioactivity of adipose tissue-derived MSCs and the potential of fucoidan-treated MSCs to improve neovascularization in ischemic tissues of CKD mice. Treatment of MSCs with fucoidan increased their proliferative potential and the expression of cell cycle-associated proteins, such as cyclin E, cyclin dependent kinase (CDK) 2, cyclin D1, and CDK4, via focal adhesion kinase and the phosphatidylinositol-4,5-bisphosphate 3-kinase-Akt axis. Moreover, fucoidan enhanced the immunomodulatory activity of MSCs through the ERK-IDO-1 signal cascade. Fucoidan was found to augment the proliferation, incorporation, and endothelial differentiation of transplanted MSCs at ischemic sites in CKD mice hind limbs. In addition, transplantation of fucoidan-treated MSCs enhanced the ratio of blood flow and limb salvage in CKD mice with hind limb ischemia. To our knowledge, our findings are the first to reveal that fucoidan enhances the bioactivity of MSCs and improves their neovascularization in ischemic injured tissues of CKD. In conclusion, fucoidan-treated MSCs may provide an important pathway toward therapeutic neovascularization in patients with CKD.
authors.affiliation: Laboratory for Vascular Medicine & Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 626-870, Republic of Korea.
authors.forename: Jun Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine and Research Institute for Veterinary Science, and BK21 PLUS Creative Veterinary Research Center, Seoul National University, Seoul 151-741, Republic of Korea; Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Republic of Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Ryu
authors.affiliation: 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.
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Han
authors.affiliation: Soonchunhyang Institute of Medi-bio Science, Soonchunhyang University, Cheonan 330-930, Republic of Korea.
authors.forename: Mohammad Farid
authors.initials: MF
authors.lastname: Zia
authors.affiliation: Soonchunhyang Institute of Medi-bio Science, Soonchunhyang University, Cheonan 330-930, Republic of Korea.
authors.forename: Hyog Young
authors.initials: HY
authors.lastname: Kwon
authors.affiliation: Department of Internal Medicine, Soonchunhyang University, Seoul, Republic of Korea; Hyonam Kidney Laboratory, Soonchunhyang University, Seoul, Republic of Korea. Electronic address: nohneph@schmc.ac.kr.
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Noh
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine and Research Institute for Veterinary Science, and BK21 PLUS Creative Veterinary Research Center, Seoul National University, Seoul 151-741, Republic of Korea. Electronic address: hjhan@snu.ac.kr.
authors.forename: Ho Jae
authors.initials: HJ
authors.lastname: Han
authors.affiliation: 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.
authors.forename: Sang Hun
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000818:Animals; D015415:Biomarkers; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases; D006614:Hindlimb / Q000098:blood supply* / Q000378:metabolism*; D006801:Humans; D007511:Ischemia / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000534:rehabilitation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D010641:Phenotype; D010766:Phosphorylation; D011134:Polysaccharides / Q000494:pharmacology*; D051436:Renal Insufficiency, Chronic / Q000150:complications*
chemical_list: D015415:Biomarkers; D011134:Polysaccharides; C007789:fucoidan; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Chronic kidney disease; Fucoidan; Ischemic disease; Mesenchymal stem cells; Neovascularization; Vascular repair