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Singapore, Singapore

Leong M.F.,Institute Of Bioengineering And Nanotechnology, Singapore | Chan W.Y.,SingHealth Research Facility | Chian K.S.,Nanyang Technological University

Background: Conventional electrospun scaffolds have very small pores, thus limiting cellular infiltration, tissue ingrowth and vascularization in tissue engineering applications. The cryogenic electrospinning process overcame the small pore size constraints found in conventional electrospun scaffolds. Aim: The aim of this paper is to propose a mechanism for cryogenic electrospinning and how scaffold pore size can be controlled. Materials & methods: We studied the roles of ice crystals in controlling the pore size of cryogenic electrospun scaffolds (CES). Based on this understanding, we have successfully fabricated a bilayered scaffold with distinctly different pore sizes. Results: Our study showed that CES pore size was dependent on the structure of the frost layer formed and hence the factors affecting ice deposition. The bilayered scaffold was able to support the coculture of human dermal fibroblasts and keratinocytes. Conclusion: The larger pores of CES add versatility to the use of electrospun scaffolds in tissue engineering applications. © 2013 Future Medicine Ltd. Source

Tang Y.,SingHealth Research Facility | Tang Y.,National University of Singapore | Li G.,SingHealth Research Facility | Li G.,National University of Singapore
Journal of Molecular Endocrinology

Dyslipidemia is a common metabolic disorder in diabetes. Nitric oxide (NO) production from endothelium plays the primary role in endothelium-mediated vascular relaxation and other endothelial functions. Therefore, we investigated the effects of elevated free fatty acids (FFA) on the stimulation of NO production by phospholipase C (PLC)-activating receptor agonists (potent physiological endothelium-dependent vasodilators) and defined the possible alterations of signaling pathways implicated in this scenario. Exposure of bovine aortic endothelial cells (BAECs) to high concentrations of a mixture of fatty acids (oleate and palmitate) for 5 or 10 days significantly reduced NO production evoked by receptor agonists (bradykinin or ATP) in a time- and dose-dependent manner. Such defects were not associated with alterations of either endothelial NO synthase mass or inositol phospholipid contents but were probably due to reduced elevations of intracellular free Ca 2+ levels ([Ca 2+] i) under these conditions. Exposure of BAECs to FFA significantly attenuated agonist-induced [Ca 2+] i increases by up to 54% in a dose- and time-dependent manner. Moreover, bradykinin receptor affinity on the cell surface was significantly decreased by high concentrations of FFA. The morphology of BAECs was altered after 10-day culture with high FFA. Co-culture with protein kinase C (PKC) inhibitors or antioxidants was able to reverse the impairments of receptor agonist-induced NO production and [Ca 2+] i rises as well as the alteration of receptor affinity in BAECs exposed to FFA. These data indicate that chronic exposure to high FFA reduces NO generation in endothelial cells probably by impairing PLC-mediated Ca 2+ signaling pathway through activation of PKC and excess generation of oxidants. © 2011 Society for Endocrinology. Source

Shao S.,SingHealth Research Facility | Shao S.,National University of Singapore | Gao Y.,National University of Singapore | Xie B.,SingHealth Research Facility | And 6 more authors.
Journal of Endocrinology

Shortage of cadaveric pancreata and requirement of immune suppression are two major obstacles in transplantation therapy of type 1 diabetes. Here, we investigate whether i.p. transplantation of alginate-encapsulated insulin-producing cells from the embryo-derived mouse embryo progenitor-derived insulin-producing-1 (MEPI-1) line could lower hyperglycemia in immune-competent, allogeneic diabetic mice. Within days after transplantation, hyperglycemia was reversed followed by about 2.5 months of normo- to moderate hypoglycemia before relapsing. Mice transplanted with unencapsulated MEPI cells relapsed within 2 weeks. Removal of the transplanted capsules by washing of the peritoneal cavity caused an immediate relapse of hyperglycemia that could be reversed with a second transplantation. The removed capsules had fibrotic overgrowth but remained permeable to 70 kDa dextrans and displayed glucose-stimulated insulin secretion. Following transplantation, the number of cells in capsules increased initially, before decreasing to below the starting cell number at 75 days. Histological examination showed that beyond day 40 post-transplantation, encapsulated cell clusters exhibited proliferating cells with a necrotic core. Blood glucose, insulin levels, and oral glucose tolerance test in the transplanted animals correlated directly with the number of viable cells remaining in the capsules. Our study demonstrated that encapsulation could effectively protect MEPI cells from the host immune system without compromising their ability to correct hyperglycemia in immune-competent diabetic mice for 2.5 months, thereby providing proof that immunoisolation of expansible but immune-incompatible stem cell-derived surrogate β-cells by encapsulation is a viable diabetes therapy. © 2011 Society for Endocrinology. Source

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