Fucoidan improves bioactivity and vasculogenic potential of mesenchymal stem cells in murine hind limb ischemia associated with chronic kidney disease. (August 2016)

• Record Type: Journal Article
• Authors: Lee, Jun Hee; Ryu, Jung Min; Han, Yong-Seok; Zia, Mohammad Farid; Kwon, Hyog Young; Noh, Hyunjin; Han, Ho Jae; Lee, Sang Hun
• Is Part Of: Journal of molecular and cellular cardiology. Volume 97(2016:Aug.)
• Page Start: 169
• Page End: 179
• Publication Date: 2016-08
• Subjects: Akt Protein kinase B (PKB) -- CDK Cyclin-dependent kinase -- CKD Chronic kidney disease -- DAPI 4′6-Diamidino-2-phenylindole -- ERK Extracellular signal-regulated kinase -- FAK Focal adhesion kinase -- HNA Human nuclear antigen -- IDO Indoleamine-pyrrole 2, 3-dioxygenase -- MSC Mesenchymal stem cells -- PCNA Proliferating cell nuclear antigen -- PI3K Phosphatidylinositol-4, 5-bisphosphate 3-kinase; Mesenchymal stem cells -- Fucoidan -- Chronic kidney disease -- Ischemic disease -- Vascular repair -- Neovascularization; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2016.05.011
• Languages: English
• ISSNs: 0022-2828

Abstract

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. Highlights: Fucoidan enhances the proliferation of MSCs through FAK-Akt axis. Fucoidan increases the immunomodulatory activity of MSCs via ERK-IDO-1 pathway. Transplantation of fucoidan-treated MSCs augments the functional recovery in CKD mice with hind limb ischemia.