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Article ; Online: Design of experiments approach to engineer cell-secreted matrices for directing osteogenic differentiation.

Decaris, Martin L / Leach, J Kent

2010 Volume 39, Issue 4, Page(s) 1174–1185

Abstract: The presentation of extracellular matrix (ECM) proteins provides an opportunity to instruct the phenotype and behavior of responsive cells. Decellularized cell-secreted matrix coatings (DM) represent a biomimetic culture surface that retains the ... ...

Abstract	The presentation of extracellular matrix (ECM) proteins provides an opportunity to instruct the phenotype and behavior of responsive cells. Decellularized cell-secreted matrix coatings (DM) represent a biomimetic culture surface that retains the complexity of the natural ECM. Microenvironmental culture conditions alter the composition of these matrices and ultimately the ability of DMs to direct cell fate. We employed a design of experiments (DOE) multivariable analysis approach to determine the effects and interactions of four variables (culture duration, cell seeding density, oxygen tension, and media supplementation) on the capacity of DMs to direct the osteogenic differentiation of human mesenchymal stem cells (hMSCs). DOE analysis revealed that matrices created with extended culture duration, ascorbate-2-phosphate supplementation, and in ambient oxygen tension exhibited significant correlations with enhanced hMSC differentiation. We validated the DOE model results using DMs predicted to have superior (DM1) or lesser (DM2) osteogenic potential for naïve hMSCs. Compared to cells on DM2, hMSCs cultured on DM1 expressed 2-fold higher osterix levels and deposited 3-fold more calcium over 3 weeks. Cells on DM1 coatings also exhibited greater proliferation and viability compared to DM2-coated substrates. This study demonstrates that DOE-based analysis is a powerful tool for optimizing engineered systems by identifying significant variables that have the greatest contribution to the target output.
MeSH term(s)	Alkaline Phosphatase/metabolism ; Biomedical Engineering ; Biomimetic Materials ; Calcium/metabolism ; Cell Adhesion ; Cell Differentiation/physiology ; Cell Proliferation ; Cell Survival ; Extracellular Matrix Proteins/physiology ; Gene Expression Regulation, Developmental ; Humans ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/physiology ; Models, Biological ; Osteoblasts/cytology ; Osteoblasts/physiology ; Osteogenesis/genetics ; Osteogenesis/physiology ; Polymerase Chain Reaction ; Tissue Engineering
Chemical Substances	Extracellular Matrix Proteins ; Alkaline Phosphatase (EC 3.1.3.1) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2010-12-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	185984-5
ISSN	1573-9686 ; 0191-5649 ; 0090-6964
ISSN (online)	1573-9686
ISSN	0191-5649 ; 0090-6964
DOI	10.1007/s10439-010-0217-x
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Zs.A 1018: Show issues

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Article ; Online: Bioceramic-mediated trophic factor secretion by mesenchymal stem cells enhances in vitro endothelial cell persistence and in vivo angiogenesis.

He, Jiawei / Decaris, Martin L / Leach, J Kent

Tissue engineering. Part A

2012 Volume 18, Issue 13-14, Page(s) 1520–1528

Abstract: Mesenchymal stem cells (MSCs) seeded in composite implants formed of hydroxyapatite (HA) and poly (lactide-co-glycolide) (PLG) exhibit increased osteogenesis and enhanced angiogenic potential. Endothelial colony-forming cells (ECFCs) can participate in ... ...

Abstract	Mesenchymal stem cells (MSCs) seeded in composite implants formed of hydroxyapatite (HA) and poly (lactide-co-glycolide) (PLG) exhibit increased osteogenesis and enhanced angiogenic potential. Endothelial colony-forming cells (ECFCs) can participate in de novo vessel formation when implanted in vivo. The aim of this study was to determine the capacity of HA-PLG composites to cotransplant MSCs and ECFCs, with the goal of accelerating vascularization and resultant bone formation. The incorporation of HA into PLG scaffolds improved the efficiency of cell seeding and ECFC survival in vitro. We observed increases in mRNA expression and secretion of potent angiogenic factors by MSCs when cultured on HA-PLG scaffolds compared to PLG controls. Upon implantation into an orthotopic calvarial defect, ECFC survival on composite scaffolds was not increased in the presence of MSCs, nor did the addition of ECFCs enhance vascularization beyond increases observed with MSCs alone. Microcomputed tomography (micro-CT) performed on explanted calvarial tissues after 12 weeks revealed no significant differences between treatment groups for bone volume fraction (BVF) or bone mineral density (BMD). Taken together, these results provide evidence that HA-containing composite scaffolds seeded with MSCs can enhance neovascularization, yet MSC-secreted trophic factors do not consistently increase the persistence of co-transplanted ECFCs.
MeSH term(s)	Animals ; Bone Density/drug effects ; Cell Line ; Ceramics/pharmacology ; Coculture Techniques ; Colony-Forming Units Assay ; DNA/metabolism ; Durapatite/pharmacology ; Endothelial Cells/drug effects ; Endothelial Cells/metabolism ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism ; Lactic Acid/pharmacology ; Luminescent Measurements ; Male ; Mesenchymal Stem Cells/drug effects ; Mesenchymal Stem Cells/metabolism ; Neovascularization, Physiologic/drug effects ; Neovascularization, Physiologic/genetics ; Osteogenesis/drug effects ; Polyglycolic Acid/pharmacology ; Polylactic Acid-Polyglycolic Acid Copolymer ; Rats ; Rats, Nude ; Skull/drug effects ; Skull/pathology ; Tissue Scaffolds/chemistry ; Up-Regulation/drug effects ; Up-Regulation/genetics ; X-Ray Microtomography
Chemical Substances	Intercellular Signaling Peptides and Proteins ; Polylactic Acid-Polyglycolic Acid Copolymer (1SIA8062RS) ; Polyglycolic Acid (26009-03-0) ; Lactic Acid (33X04XA5AT) ; DNA (9007-49-2) ; Durapatite (91D9GV0Z28)
Language	English
Publishing date	2012-06-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2420582-5
ISSN	1937-335X ; 1937-3341
ISSN (online)	1937-335X
ISSN	1937-3341
DOI	10.1089/ten.TEA.2011.0127
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Article ; Online: Alginate hydrogels containing cell-interactive beads for bone formation.

Bhat, Archana / Hoch, Allison I / Decaris, Martin L / Leach, J Kent

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2013 Volume 27, Issue 12, Page(s) 4844–4852

Abstract: Alginate hydrogels containing cell-instructive cues are the subject of intense interest for their use as cell carriers in bone tissue engineering. Peptides and proteins are chemically grafted onto these hydrophilic materials to facilitate adhesion and ... ...

Abstract	Alginate hydrogels containing cell-instructive cues are the subject of intense interest for their use as cell carriers in bone tissue engineering. Peptides and proteins are chemically grafted onto these hydrophilic materials to facilitate adhesion and direct phenotype of entrapped cells. However, the presentation of a single or small number of peptides does not represent the complexity of the native extracellular matrix (ECM) of bony tissues. Mesenchymal stem cells (MSCs) secrete ECM that can be harvested and deposited on various substrata to promote osteogenic differentiation. In this study, we hypothesized that the presentation of engineered cell-secreted ECM on microbeads suspended in alginate hydrogels would promote cell adhesion and enhance osteogenic differentiation of undifferentiated MSCs without chemical incorporation of cell-adhesive peptides. Human MSCs entrapped in alginate hydrogels loaded with ECM-coated beads showed increased interaction with beads, when compared with cells suspended in hydrogels containing uncoated blank (BLK) beads. MSCs entrapped in ECM gels exhibited increased alkaline phosphatase (ALP) activity and expression of osteogenic genes in vitro compared with hydrogels modified with arginine-glycine-aspartic acid (RGD)-containing peptides. Transplantation of MSCs into an ectopic site resulted in significant increases in blood vessel density for ECM hydrogels when compared with the BLK or RGD gels. Furthermore, we observed comparable levels of bone formation at 6 wk with ECM and RGD hydrogels. These findings demonstrate that engineered ECM can be deployed in a minimally invasive manner to direct the formation of bony tissue. This strategy may provide an alternative to the engraftment of proteins or peptides onto the polymer backbone of hydrogels for directing cellular behavior.
MeSH term(s)	Alginates/pharmacology ; Alkaline Phosphatase/metabolism ; Animals ; Biocompatible Materials/chemistry ; Biocompatible Materials/pharmacology ; Extracellular Matrix/metabolism ; Humans ; Hydrogels/chemistry ; Hydrogels/pharmacology ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells/cytology ; Mesenchymal Stromal Cells/drug effects ; Mesenchymal Stromal Cells/metabolism ; Microspheres ; Oligopeptides/pharmacology ; Osteogenesis/drug effects ; Rats
Chemical Substances	Alginates ; Biocompatible Materials ; Hydrogels ; Oligopeptides ; arginyl-glycyl-aspartic acid (78VO7F77PN) ; Alkaline Phosphatase (EC 3.1.3.1)
Language	English
Publishing date	2013-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.12-213611
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Zs.A 2266: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Reversal of TGFβ1-Driven Profibrotic State in Patients with Pulmonary Fibrosis.

Chapman, Harold A / Wei, Ying / Montas, Genevieve / Leong, Darren / Golden, Jeffrey A / Trinh, Binh N / Wolters, Paul J / Le Saux, Claude J / Jones, Kirk D / Hills, Nancy K / Foster, Elena / Oldham, Justin M / Linderholm, Angela L / Kotak, Prerna / Decaris, Martin / Turner, Scott / Song, Jin-Woo

The New England journal of medicine

2020 Volume 382, Issue 11, Page(s) 1068–1070

MeSH term(s)	Antioxidants/administration & dosage ; Biomarkers/metabolism ; Biopsy ; Catechin/analogs & derivatives ; Catechin/therapeutic use ; Collagen Type I/metabolism ; Humans ; Pulmonary Fibrosis/drug therapy ; Pulmonary Fibrosis/pathology ; Snail Family Transcription Factors/metabolism ; Transforming Growth Factor beta1/drug effects ; Transforming Growth Factor beta1/physiology
Chemical Substances	Antioxidants ; Biomarkers ; Collagen Type I ; SNAI1 protein, human ; Snail Family Transcription Factors ; TGFB1 protein, human ; Transforming Growth Factor beta1 ; Catechin (8R1V1STN48) ; epigallocatechin gallate (BQM438CTEL)
Language	English
Publishing date	2020-03-23
Publishing country	United States
Document type	Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc1915189
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Article ; Online: Transferable cell-secreted extracellular matrices enhance osteogenic differentiation.

Decaris, Martin L / Mojadedi, Azad / Bhat, Archana / Leach, J Kent

Acta biomaterialia

2012 Volume 8, Issue 2, Page(s) 744–752

Abstract: The coating of synthetic biomaterials with cell-derived decellularized extracellular matrices (DMs) represents a promising approach to confer bioactivity to otherwise inert materials and direct cell fate of host or transplanted cells. These coatings are ... ...

Abstract	The coating of synthetic biomaterials with cell-derived decellularized extracellular matrices (DMs) represents a promising approach to confer bioactivity to otherwise inert materials and direct cell fate of host or transplanted cells. These coatings are typically deposited on biomaterials by culturing matrix-depositing cells for a sufficient duration on the target, followed by decellularization of the substrate. We hypothesized that DMs created in monolayer culture could be collected and then transferred to a secondary substrate while retaining their instructive potential. Transferred decellularized matrices (tDMs) were created by culturing human mesenchymal stem cells (hMSCs) on tissue culture plastic (TCP) under a controlled microenvironment to deposit a highly osteogenic DM, followed by collection, mechanical homogenization and transfer to a secondary culture surface. We then investigated its capacity to accelerate naïve hMSC osteogenic differentiation by quantifying gene expression, intracellular alkaline phosphatase production, and calcium deposition when cultured on DMs or tDMs. All markers were significantly higher in hMSCs seeded on DMs or tDMs compared to cells on TCP. The osteogenic response of naïve hMSCs to tDMs was dose dependent. We observed a reduction in ERK phosphorylation in hMSCs, as well as a possible role of the cell surface integrin α2β1, when probing the mode of efficacy for tDMs. This study represents a proof-of-principle that cell-derived matrix coatings can be deposited and effectively transferred while retaining the ability to instruct cell phenotype, thus offering a novel approach toward the development of hybrid biomaterials that mimic the complex interactions between cells and the extracellular matrix.
MeSH term(s)	Alkaline Phosphatase/metabolism ; Anthraquinones/metabolism ; Cell Adhesion ; Cell Differentiation ; Cell Shape ; Cells, Cultured ; Extracellular Matrix/metabolism ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Gene Expression Regulation ; Humans ; Immunohistochemistry ; Integrins/metabolism ; Intracellular Space/enzymology ; Mesenchymal Stromal Cells/cytology ; Mesenchymal Stromal Cells/enzymology ; Mesenchymal Stromal Cells/secretion ; Osteogenesis ; Phosphorylation ; Polymerase Chain Reaction ; Signal Transduction
Chemical Substances	Anthraquinones ; Integrins ; alizarin (60MEW57T9G) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; Alkaline Phosphatase (EC 3.1.3.1)
Language	English
Publishing date	2012-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2011.10.035
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Article ; Online: Dual inhibition of α

Decaris, Martin L / Schaub, Johanna R / Chen, Chun / Cha, Jacob / Lee, Gail G / Rexhepaj, Megi / Ho, Steve S / Rao, Vikram / Marlow, Megan M / Kotak, Prerna / Budi, Erine H / Hooi, Lisa / Wu, Jianfeng / Fridlib, Marina / Martin, Shamra P / Huang, Shaoyi / Chen, Ming / Muñoz, Manuel / Hom, Timothy F /

Wolters, Paul J / Desai, Tushar J / Rock, Fernando / Leftheris, Katerina / Morgans, David J / Lepist, Eve-Irene / Andre, Patrick / Lefebvre, Eric A / Turner, Scott M

Respiratory research

2021 Volume 22, Issue 1, Page(s) 265

Abstract: Rationale: α: Objectives: We evaluated multiple α: Methods: Selective α: Measurements and main results: Inhibition of integrins α: Conclusions: In the fibrotic lung, dual inhibition of integrins ... ...

Abstract	Rationale: α Objectives: We evaluated multiple α Methods: Selective α Measurements and main results: Inhibition of integrins α Conclusions: In the fibrotic lung, dual inhibition of integrins α
MeSH term(s)	Animals ; Antifibrotic Agents/pharmacology ; Bleomycin ; Cell Line ; Coculture Techniques ; Collagen Type I, alpha 1 Chain/genetics ; Collagen Type I, alpha 1 Chain/metabolism ; Disease Models, Animal ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Humans ; Idiopathic Pulmonary Fibrosis/drug therapy ; Idiopathic Pulmonary Fibrosis/genetics ; Idiopathic Pulmonary Fibrosis/metabolism ; Idiopathic Pulmonary Fibrosis/pathology ; Integrin alpha6beta1/antagonists & inhibitors ; Integrin alpha6beta1/metabolism ; Lung/drug effects ; Lung/metabolism ; Lung/pathology ; Mice, Inbred C57BL ; Phosphorylation ; Receptors, Vitronectin/antagonists & inhibitors ; Receptors, Vitronectin/metabolism ; Signal Transduction ; Smad3 Protein/metabolism ; Mice
Chemical Substances	Antifibrotic Agents ; COL1A1 protein, human ; Col1a1 protein, mouse ; Collagen Type I, alpha 1 Chain ; Integrin alpha6beta1 ; Receptors, Vitronectin ; Smad3 Protein ; Smad3 protein, mouse ; integrin alphavbeta1 ; Bleomycin (11056-06-7)
Language	English
Publishing date	2021-10-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-993X
ISSN (online)	1465-993X
ISSN	1465-993X
DOI	10.1186/s12931-021-01863-0
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Article ; Online: Oxygen tension modulates neurite outgrowth in PC12 cells through a mechanism involving HIF and VEGF.

Genetos, Damian C / Cheung, Whitney K / Decaris, Martin L / Leach, J Kent

Journal of molecular neuroscience : MN

2010 Volume 40, Issue 3, Page(s) 360–366

Abstract: Cell-based approaches are a promising therapeutic strategy for treating injuries to the nervous system, but the optimal means to promote neurite extension and direct cellular behavior are unclear. Previous studies have examined the behavior of neural- ... ...

Abstract	Cell-based approaches are a promising therapeutic strategy for treating injuries to the nervous system, but the optimal means to promote neurite extension and direct cellular behavior are unclear. Previous studies have examined the behavior of neural-like cells in ambient air (21% oxygen tension), yet these conditions are not representative of the physiological oxygen microenvironment of neural tissues. We hypothesized that neuronal differentiation of a model neural cell line (PC12) could be controlled by modulating local oxygen tension. Compared to ambient conditions, PC12 cells cultured in reduced oxygen exhibited significant increases in neurite extension and total neurite length, with 4% oxygen yielding the highest levels of both indicators. We confirmed neurite extension was mediated through oxygen-responsive mechanisms using small molecules that promote or inhibit HIF-1alpha stabilization. The hypoxic target gene Vegf was implicated as a neurotrophic factor, as neurite formation at 21% oxygen was mimicked with exogenous VEGF, and a VEGF-neutralizing antibody attenuated neurite formation under reduced oxygen conditions. These findings demonstrate that behavior of neural-like cells is driven by the oxygen microenvironment via VEGF function, and suggest promising approaches for future applications in neural repair.
MeSH term(s)	Animals ; Cell Differentiation/physiology ; Humans ; Hypoxia/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Neurites/metabolism ; Neurites/ultrastructure ; Oxygen/metabolism ; PC12 Cells/cytology ; PC12 Cells/metabolism ; Rats ; Signal Transduction/physiology ; Vascular Endothelial Growth Factors/metabolism
Chemical Substances	Hypoxia-Inducible Factor 1, alpha Subunit ; Vascular Endothelial Growth Factors ; Oxygen (S88TT14065)
Language	English
Publishing date	2010-01-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1043392-2
ISSN	1559-1166 ; 0895-8696
ISSN (online)	1559-1166
ISSN	0895-8696
DOI	10.1007/s12031-009-9326-0
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Zs.A 3006: Show issues

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Article: Transferable cell-secreted extracellular matrices enhance osteogenic differentiation

Decaris, Martin L / Mojadedi, Azad / Bhat, Archana / Leach, J. Kent

Acta Biomaterialia. 2012 Feb., v. 8, no. 2

2012

Abstract	The coating of synthetic biomaterials with cell-derived decellularized extracellular matrices (DMs) represents a promising approach to confer bioactivity to otherwise inert materials and direct cell fate of host or transplanted cells. These coatings are typically deposited on biomaterials by culturing matrix-depositing cells for a sufficient duration on the target, followed by decellularization of the substrate. We hypothesized that DMs created in monolayer culture could be collected and then transferred to a secondary substrate while retaining their instructive potential. Transferred decellularized matrices (tDMs) were created by culturing human mesenchymal stem cells (hMSCs) on tissue culture plastic (TCP) under a controlled microenvironment to deposit a highly osteogenic DM, followed by collection, mechanical homogenization and transfer to a secondary culture surface. We then investigated its capacity to accelerate naïve hMSC osteogenic differentiation by quantifying gene expression, intracellular alkaline phosphatase production, and calcium deposition when cultured on DMs or tDMs. All markers were significantly higher in hMSCs seeded on DMs or tDMs compared to cells on TCP. The osteogenic response of naïve hMSCs to tDMs was dose dependent. We observed a reduction in ERK phosphorylation in hMSCs, as well as a possible role of the cell surface integrin α₂β₁, when probing the mode of efficacy for tDMs. This study represents a proof-of-principle that cell-derived matrix coatings can be deposited and effectively transferred while retaining the ability to instruct cell phenotype, thus offering a novel approach toward the development of hybrid biomaterials that mimic the complex interactions between cells and the extracellular matrix.
Keywords	alkaline phosphatase ; biocompatible materials ; bone formation ; calcium ; coatings ; extracellular matrix ; gene expression ; homogenization ; humans ; integrins ; mitogen-activated protein kinase ; phenotype ; phosphorylation ; plastics ; stem cells ; tissue culture
Language	English
Dates of publication	2012-02
Size	p. 744-752.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2011.10.035
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Article ; Online: Cell-derived matrix coatings for polymeric scaffolds.

Decaris, Martin L / Binder, Bernard Y / Soicher, Matthew A / Bhat, Archana / Leach, J Kent

Tissue engineering. Part A

2012 Volume 18, Issue 19-20, Page(s) 2148–2157

Abstract: Cells in culture deposit a complex extracellular matrix that remains intact following decellularization and possesses the capacity to modulate cell phenotype. The direct application of such decellularized matrices (DMs) to 3D substrates is problematic, ... ...

Abstract	Cells in culture deposit a complex extracellular matrix that remains intact following decellularization and possesses the capacity to modulate cell phenotype. The direct application of such decellularized matrices (DMs) to 3D substrates is problematic, as transport issues influence the homogeneous deposition, decellularization, and modification of DM surface coatings. In an attempt to address this shortcoming, we hypothesized that DMs deposited by human mesenchymal stem cells (MSCs) could be transferred to the surface of polymeric scaffolds while maintaining their capacity to direct cell fate. The ability of the transferred DM (tDM)-coated scaffolds to enhance the osteogenic differentiation of undifferentiated and osteogenically induced MSCs under osteogenic conditions in vitro was confirmed. tDM-coated scaffolds increased MSC expression of osteogenic marker genes (BGLAP, IBSP) and intracellular alkaline phosphatase production. In addition, undifferentiated MSCs deposited significantly more calcium when seeded onto tDM-coated scaffolds compared with control scaffolds. MSC-seeded tDM-coated scaffolds subcutaneously implanted in nude rats displayed significantly higher blood vessel density after 2 weeks compared with cells on uncoated scaffolds, but we did not observe significant differences in mineral deposition after 8 weeks. These data demonstrate that DM-coatings produced in 2D culture can be successfully transferred to 3D substrates and retain their capacity to modulate cell phenotype.
MeSH term(s)	Cells, Cultured ; Humans ; Mesenchymal Stromal Cells/cytology ; Osteogenesis/physiology ; Polymers ; Tissue Scaffolds
Chemical Substances	Polymers
Language	English
Publishing date	2012-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2420582-5
ISSN	1937-335X ; 1937-3341
ISSN (online)	1937-335X
ISSN	1937-3341
DOI	10.1089/ten.TEA.2011.0677
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Zs.A 5500/A: Show issues

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Article ; Online: Identifying nonalcoholic fatty liver disease patients with active fibrosis by measuring extracellular matrix remodeling rates in tissue and blood.

Decaris, Martin L / Li, Kelvin W / Emson, Claire L / Gatmaitan, Michelle / Liu, Shanshan / Wang, Yenny / Nyangau, Edna / Colangelo, Marc / Angel, Thomas E / Beysen, Carine / Cui, Jeffrey / Hernandez, Carolyn / Lazaro, Len / Brenner, David A / Turner, Scott M / Hellerstein, Marc K / Loomba, Rohit

Hepatology (Baltimore, Md.)

2017 Volume 65, Issue 1, Page(s) 78–88

Abstract: Excess collagen synthesis (fibrogenesis) in the liver plays a causal role in the progression of nonalcoholic fatty liver disease (NAFLD). Methods are needed to identify patients with more rapidly progressing disease and to demonstrate early response to ... ...

Abstract	Excess collagen synthesis (fibrogenesis) in the liver plays a causal role in the progression of nonalcoholic fatty liver disease (NAFLD). Methods are needed to identify patients with more rapidly progressing disease and to demonstrate early response to treatment. We describe here a novel method to quantify hepatic fibrogenesis flux rates both directly in liver tissue and noninvasively in blood. Twenty-one patients with suspected NAFLD ingested heavy water ( Conclusion: Using a well-characterized cohort of patients with biopsy-proven NAFLD, this study demonstrates that hepatic scar in NASH is actively remodeled even in advanced fibrosis, a disease that is generally regarded as static and slowly progressive. Moreover, hepatic collagen FSR correlates with established risks for fibrotic disease progression in NASH, and plasma lumican FSR correlates with hepatic collagen FSR, suggesting applications as direct or surrogate markers, respectively, of hepatic fibrogenesis in humans. (Hepatology 2017;65:78-88).
MeSH term(s)	Biopsy ; Collagen/metabolism ; Disease Progression ; Extracellular Matrix/metabolism ; Female ; Humans ; Liver/metabolism ; Liver/pathology ; Liver Cirrhosis/blood ; Liver Cirrhosis/complications ; Liver Cirrhosis/pathology ; Lumican/blood ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/complications
Chemical Substances	Lumican ; Collagen (9007-34-5)
Language	English
Publishing date	2017-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.28860
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