24,403 research outputs found
Stem and progenitor cells in wound healing
As more patients with large body surface area burns are surviving and requiring reconstructive surgery, there is a necessity for advances in the provision of bioengineered alternatives to autologous skin cover. The aims of this Thesis are to identify feasible source tissues of Endothelial Colony Forming Cells and Mesenchymal Stem/Stromal Cells for microvascular network formation in vitro with three-dimensional dermal substitute scaffolds. The working hypothesis is that pre-vascularised dermal scaffolds will result in better quality scarring when used with split thickness skin grafts. Human umbilical cord blood, peripheral blood and adipose tissue were collected and processed with ethical approval and informed consent. Samples were cultured to form endothelial outgrowth colonies and confluent Mesenchymal Stem/Stromal Cells, which were characterised using flow cytometry and expanded in vitro. Mesenchymal Stem/Stromal Cell multipotency was confirmed with tri-lineage mesenchymal differentiation. Primary cells were tested in a two-dimensional tubule formation co-culture assay and differences assessed using a proangiogenic antibody array. Tubule formation was tested in four different acellular dermal substitute scaffolds; Integra® Dermal Regeneration Template, Matriderm®, Neuskin-F® and De-cellularised Human Cadaveric Dermis. Umbilical cord blood was the most reliable source of Endothelial Colony Forming Cells, the yield of which could be predicted from placental weight. Microvasculature dissected free from adipose tissue was a reliable source of Mesenchymal Stem/Stromal Cells which supported significantly more tubule formation than Mesenchymal Stem/Stromal Cells from whole adipose tissue. Microvasculature Mesenchymal Stem/Stromal Cells secreted significantly higher levels of the proangiogenic hormone leptin, and addition of exogenous leptin to the tubule formation assay resulted in significantly increased tubule formation. Microvasculature was cultured in all four of the scaffolds tested, but depth of penetration was limited to 100µm. The artificial oxygen carrier perfluorocarbon was shown to increase two-dimensional tubule formation and may be useful in further three-dimensional scaffolds studies to improve microvascular penetration
Bone Marrow Stem Cell Treatment for Ischemic Heart Disease in Patients with No Option of Revascularization: A Systematic Review and Meta-Analysis
PMCID: PMC3686792This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Functional characterisation of cardiac progenitors from patients with ischaemic heart disease
Ischaemic heart disease (IHD) is the leading cause of death worldwide. Currently, even optimal medical therapies do not attenuate deterioration of the left ventricular (LV) function completely. Stem cell therapies, and recently cardiac stem cell therapies, have emerged as potential novel treatments for IHD. However, clinical evidence from randomised controlled studies has shown mixed results. Thus understanding what patient-related factors may affect the therapeutic performance of the cells may help improving treatment outcomes. The studies described in this thesis aim to understand how cardiac progenitor cells (CPCs) can re-vascularise ischaemic myocardium and promote functional repair of the heart. Resident CPCs were isolated and expanded from the right atrial appendage of 68 patients following the ‘cardiosphere’ method (cardiosphere-derived cells or CDCs). They resemble mesenchymal progenitors as they lack the expression of endothelial and haematopoietic cell surface markers but express mesenchymal progenitor cell markers (e.g. CD105, CD90). Cell function was evaluated by support of angiogenesis, mesenchymal lineage differentiation potential in vitro, and improvement in heart function in vivo. Notably in vitro, CDC from different patients differed in their angiogenic supportive and differentiation potentials. In a rodent model of myocardial infarction (MI), transplantation of CDC reduced infarct size significantly (p<0.05). However, only those CDCs with a robust pro-angiogenic ability in vitro improved vessel density and heart systolic function (p<0.05) in vivo. A multiple regression model, which accounted for 51% of the variability observed, identified New York Heart Association (NYHA) class, smoking, hypertension, type of ischaemic disease and diseased vessel as independent predictors of angiogenesis. In addition, gene expression analyses revealed that differential gene expression of several extracellular matrix components (e.g. CUX1, COL1A2, BMP1 genes and microRNA-29b) could explain the differences observed in CDC’s vascular supportive function. In summary, this is the first description of variability in the pro-angiogenic and differentiation potential of CDCs and its correlation with their therapeutic potential. This study indicates that patient stratification may need to be included in the design of future trials to improve the efficacy of cell-based therapies
Mesenchymal stromal cell therapy as treatment for ischemic heart failure: the MSC-HF study
Stem and Progenitor Cells in Wound Healing
As more patients with large body surface area burns are surviving and requiring reconstructive surgery, there is a necessity for advances in the provision of bioengineered alternatives to autologous skin cover. The aims of this Thesis are to identify feasible source tissues of Endothelial Colony Forming Cells and Mesenchymal Stem/Stromal Cells for microvascular network formation in vitro with three-dimensional dermal substitute scaffolds. The working hypothesis is that pre-vascularised dermal scaffolds will result in better quality scarring when used with split thickness skin grafts.
Human umbilical cord blood, peripheral blood and adipose tissue were collected and processed with ethical approval and informed consent. Samples were cultured to form endothelial outgrowth colonies and confluent Mesenchymal Stem/Stromal Cells, which were characterised using flow cytometry and expanded in vitro. Mesenchymal Stem/Stromal Cell multipotency was confirmed with tri-lineage mesenchymal differentiation. Primary cells were tested in a two-dimensional tubule formation co-culture assay and differences assessed using a proangiogenic antibody array. Tubule formation was tested in four different acellular dermal substitute scaffolds; Integra® Dermal Regeneration Template, Matriderm®, Neuskin-F® and De-cellularised Human Cadaveric Dermis.
Umbilical cord blood was the most reliable source of Endothelial Colony Forming Cells, the yield of which could be predicted from placental weight. Microvasculature dissected free from adipose tissue was a reliable source of Mesenchymal Stem/Stromal Cells which supported significantly more tubule formation than Mesenchymal Stem/Stromal Cells from whole adipose tissue. Microvasculature Mesenchymal Stem/Stromal Cells secreted significantly higher levels of the proangiogenic hormone leptin, and addition of exogenous leptin to the tubule formation assay resulted in significantly increased tubule formation. Microvasculature was cultured in all four of the scaffolds tested, but depth of penetration was limited to 100µm. The artificial oxygen carrier perfluorocarbon was shown to increase two-dimensional tubule formation and may be useful in further three-dimensional scaffolds studies to improve microvascular penetration.This thesis is not currently available on ORA
Jack Alive / Martin Dead : The Location of the "Author" in Jack London\u27s Martin Eden
This essay is an attempt to read Martin Eden, Jack Londonʼs autobiographical novel, in terms of the inextricable relationship between the author and the protagonist. Critics have often taken the unbalanced plot and the lack of ironic distance between narrator and character in Martin Eden as the technical weakness of London, but this paper argues that the achievement of this novel owes a great deal to the attachment of London to Martin. The unbalanced structure is a necessary product of the severe struggle of the author to kill his romantic alter ego. // Martin, who aspires to win Ruth Morse, tries to cross class boundaries by making a career of a writer. Even after realizing the emptiness of Ruth, who turns out to be nothing but a typical figure of the bourgeoisie, he somehow persists in loving her. The notion underlying here is that, for Martin, love, career and art are fundamentally inseparable. He objects to the aestheteʼs view of Brissenden on account of his separation of art from career. Martinʼs identity and life consist only in the triunity of love/career/art; the alternative is the repudiation of life. Thus, the unnatural delay of his disappointment in love can be regarded as Londonʼs strategy to set the suicide of Martin as the necessary consequence of the story. // By finishing the story and killing Martin, London finally detaches himself from Martin, reconstructs his self, and, unlike Martin, survives as a professional writer. In this sense, Martin Eden is a story about “writerʼs self-reconstruction.
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Letter from Martin Chizzick
Congratulations to Duane Pearsall for receiving the Enterpreneur of the Year award; note on the letter was written by Pearsall and it mentions that Martin, the author of the letter, died in a airplane accident
Robert Martin Tiffin's Mystery Man Newspaper Articles
Advertiser-Tribune newspaper clippings featuring a story about Robert Martin (written by Nancy Kleinhenz), a local author from Tiffin (Ohio) who wrote under the pseudonym of Lee Roberts, and two of his short stories. Martin wrote mystery novels in his spare time, creating more than 22 mystery novels. For more information about Robert Martin and a list of books go to http://www.mysteryfile.com/RMartin/JBennett.html
Intermediate filaments and the function of the dystrophin-protein complex
Intermediate filament (IF) proteins and the dystrophin-associated protein complex (DPC) play important roles in cardiac and skeletal muscle. Both systems are mutated in several different forms of inherited muscular dystrophy and cardiomyopathy. Recently two articles have been published that propose a physical link between the DPC and the IF network in muscle. Two novel IF proteins, syncoilin and desmuslin, have been identified as binding partners for the dystrophin-associated protein, α-dystrobrevin, in muscle. These novel interactions suggest that α-dystrobrevin may tether the IF protein network to the DPC. Mice lacking α-dystrobrevin develop muscular dystrophy without perturbing the assembly of the DPC at the muscle membrane, suggesting the involvement of other non-DPC proteins in the disease. The interaction between the DPC and the IF network may be disrupted in patients with Duchenne muscular dystrophy and in mice lacking α-dystrobrevin
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