|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | COMP-Ang1, a Variant of Angiopoietin 1, Inhibits Serum-Deprived Apoptosis of Mesenchymal Cells via PI3K/Akt and Mitogen-Activated Protein Kinase Pathways. Pharmacology. 2010 Nov 29;86(5-6):327-335 Authors: Lee KN, Seo MC, Bae IH, Oh SH, Jang WG, Jeong BC, Oh WM, Kim SH, Lee SE, Shim KM, Park BK, Koh JT Background/Aims: Cartilage oligomeric matrix protein (COMP)-angiopoietin 1 (Ang1) is a soluble and stable form of Ang1 which plays important roles in vessel formation and the survival of endothelial cells, neurons and cardiomyocytes. However, the effects of COMP-Ang1 on the survival of mesenchymal cells are unknown. Mesenchymal cells have been transplanted with some scaffolds for bone tissue regeneration, but they occasionally underwent cell death due to a lack of nutrient supply. This study examined the effects of COMP-Ang1 on the survival of mesenchymal cells under nutrient-deprived conditions. Methods: Primary and C3H10T1/2 mesenchymal cells were cultured under serum deprivation with or without COMP-Ang1. The effects of COMP-Ang1 on mesenchymal cell survival and its molecular mechanism were determined using a viability test, RT-PCR, Western blotting and fluorescence-activated cell sorting analysis. Results and Conclusion: COMP-Ang1 inhibited the nutrient-deprived apoptotic cell death of mesenchymal cells through the Akt, p38 and extracellular-signal-regulated kinase (ERK) pathways. In addition, COMP-Ang1 reversed the nutrient-deprived suppression of cyclin D1 mRNA expression. These results suggest that COMP-Ang1 has a protective role in the survival of nutrient-deprived mesenchymal cells. The use of COMP-Ang1 with some scaffolds might be useful for bone tissue engineering. PMID: 21109762 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Fabrication and hemocompatibility of cell outer membrane mimetic surfaces on chitosan by layer by layer assembly with polyanion bearing phosphorylcholine groups. Colloids Surf B Biointerfaces. 2010 Nov 5; Authors: Gong M, Wang YB, Li M, Hu BH, Gong YK Three random copolymers poly(2-methacryloyloxyethyl phosphorylcholine-co-methacrylic acid) (PMAs) were synthesized by free radical polymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) and methacrylic acid (MA) with different monomer ratios under monomer-starved conditions. The synthesized PMA polyanions were assembled on chitosan (CS) film surfaces via electrostatic interactions. Using layer by layer (LbL) assembly with PMA polyanion and chitosan polycation, PMA/CS multilayer thin films with phosphorylcholine groups on the outer surfaces were fabricated. The modified surfaces were characterized by dynamic contact angle (DCA), X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). Hemocompatibility of the surfaces was estimated by protein adsorption and platelet adhesion measurements. The results indicated that cell outer membrane mimetic structures were formed on the modified surfaces with PMA as the outermost layer, and the hemocompatibility of the modified surfaces was significantly improved. This facile method of fabricating cell outer membrane mimetic surfaces may have potential applications in the fields of hemocompatible coatings, drug delivery, and tissue engineering. PMID: 21109407 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Modulation of Embryonic Mesenchymal Progenitor Cell Differentiation via Control over Pure Mechanical Modulus in Electrospun Nanofibers. Acta Biomater. 2010 Nov 22; Authors: Nam J, Johnson J, Lannutti JJ, Agarwal S As the potential range of stem cell applications in tissue engineering continues to grow, appropriate scaffolding choice is necessary to create tightly defined artificial microenvironments for each target organ. These microenvironments determine stem cell fate via control over differentiation. In this study, we examined the specific effects of scaffold stiffness on embryonic mesenchymal progenitor cell behavior. Mechanically distinct scaffolds having identical microstructure and surface chemistry, were produced utilizing core-shell electrospinning. The modulus of core-shell poly(ether sulfone)-poly(ε-caprolactone) (PES-PCL) fibers (30.6 MPa) was more than 4 times that of pure PCL (7.1 MPa). Results from chondrogenic or osteogenic differentiation of progenitor cells on each scaffold indicate that the lower modulus PCL fibers provided more appropriate microenvironments for chondrogenesis, evident by marked upregulation of chondrocytic Sox9, collagen type 2 and aggrecan gene expression, and chondrocyte-specific extracellular matrix glycosaminoglycan production. In contrast, the stiffer core-shell PES-PCL fibers supported enhanced osteogenesis by promoting osteogenic Runx2, alkaline phosphatase and osteocalcin gene expression as well as alkaline phosphatase activity. The findings demonstrate that the microstructural stiffness of a scaffold and the pliability of individual fibers may play a critical role in controlling stem cell differentiation. This may occur via regulation of distinct cytoskeletal organization and subsequent intracellular signaling events that control differentiation-specific gene expression. PMID: 21109030 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | NKX6.1 Promotes PDX-1-Induced Liver to Pancreatic β-Cells Reprogramming. Cell Reprogram. 2010 Dec;12(6):655-64 Authors: Gefen-Halevi S, Rachmut IH, Molakandov K, Berneman D, Mor E, Meivar-Levy I, Ferber S Abstract Reprogramming adult mammalian cells is an attractive approach for generating cell-based therapies for degenerative diseases, such as diabetes. Adult human liver cells exhibit a high level of developmental plasticity and have been suggested as a potential source of pancreatic progenitor tissue. An instructive role for dominant pancreatic transcription factors in altering the hepatic developmental fate along the pancreatic lineage and function has been demonstrated. Here we analyze whether transcription factors expressed in mature pancreatic β-cells preferentially activate β-cell lineage differentiation in liver. NKX6.1 is a transcription factor uniquely expressed in β-cells of the adult pancreas, its potential role in reprogramming liver cells to pancreatic lineages has never been analyzed. Our results suggest that NKX6.1 activates immature pancreatic markers such as NGN-3 and ISL-1 but not pancreatic hormones gene expression in human liver cells. We hypothesized that its restricted capacity to activate a wide pancreatic repertoire in liver could be related to its incapacity to activate endogenous PDX-1 expression in liver cells. Indeed, the complementation of NKX6.1 by ectopic PDX-1 expression substantially and specifically promoted insulin expression and glucose regulated processed hormone secretion to a higher extent than that of PDX-1 alone, without increasing the reprogrammed cells. This may suggest a potential role for NKX6.1 in promoting PDX-1 reprogrammed cells maturation along the β-cell-like lineage. By contrast, NKX6.1 repressed PDX-1 induced proglucagon gene expression. The individual and concerted effects of pancreatic transcription factors in adult extra-pancreatic cells, is expected to facilitate developing regenerative medicine approaches for cell replacement therapy in diabetics. PMID: 21108535 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | The significance of copper chelators in clinical and experimental application. J Nutr Biochem. 2010 Nov 24; Authors: Ding X, Xie H, Kang YJ The essentiality and redox-activity of copper make it indispensable in the mammalian system. However, a comprehensive understanding of copper metabolism and function has not been achieved. Copper chelators have been used as an approach to provide insights into copper acquisition, distribution, and disposition at both the cellular and organism level. Unfortunately, the understanding of effective copper chelators is predominantly based upon their chemical structures and their reactions with copper. The understanding of the efficacy of copper chelators in the biological system has been equivocal, thereby leading to under- or misleading-utilization of these agents in clinical and experimental approaches. Current use of copper chelators in vivo almost exclusively either limits the availability or focuses on the removal of copper in mammalian organ system. There are at least two aspects of copper chelators that are yet to be explored. First, copper chelators preferentially bind either cuprous or cupric. As a result, they potentially modulate copper redox-activity without removing copper from the system. Second, copper chelators are characterized as either membrane-permeable or -impermeable, thus would serve as an organ-selective copper delivery or deprivation system to manipulate the biological function of copper. Here we review clinically relevant copper chelators that have been experimentally or clinically studied for their role in manipulation of copper metabolism and function, paying critical attention to potentially more valuable usage of these agents. PMID: 21109416 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | NKX6.1 Promotes PDX-1-Induced Liver to Pancreatic β-Cells Reprogramming. Cell Reprogram. 2010 Dec;12(6):655-64 Authors: Gefen-Halevi S, Rachmut IH, Molakandov K, Berneman D, Mor E, Meivar-Levy I, Ferber S Abstract Reprogramming adult mammalian cells is an attractive approach for generating cell-based therapies for degenerative diseases, such as diabetes. Adult human liver cells exhibit a high level of developmental plasticity and have been suggested as a potential source of pancreatic progenitor tissue. An instructive role for dominant pancreatic transcription factors in altering the hepatic developmental fate along the pancreatic lineage and function has been demonstrated. Here we analyze whether transcription factors expressed in mature pancreatic β-cells preferentially activate β-cell lineage differentiation in liver. NKX6.1 is a transcription factor uniquely expressed in β-cells of the adult pancreas, its potential role in reprogramming liver cells to pancreatic lineages has never been analyzed. Our results suggest that NKX6.1 activates immature pancreatic markers such as NGN-3 and ISL-1 but not pancreatic hormones gene expression in human liver cells. We hypothesized that its restricted capacity to activate a wide pancreatic repertoire in liver could be related to its incapacity to activate endogenous PDX-1 expression in liver cells. Indeed, the complementation of NKX6.1 by ectopic PDX-1 expression substantially and specifically promoted insulin expression and glucose regulated processed hormone secretion to a higher extent than that of PDX-1 alone, without increasing the reprogrammed cells. This may suggest a potential role for NKX6.1 in promoting PDX-1 reprogrammed cells maturation along the β-cell-like lineage. By contrast, NKX6.1 repressed PDX-1 induced proglucagon gene expression. The individual and concerted effects of pancreatic transcription factors in adult extra-pancreatic cells, is expected to facilitate developing regenerative medicine approaches for cell replacement therapy in diabetics. PMID: 21108535 [PubMed - in process] | | | | | | | | | |  | |  | |  |
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