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3 results on '"ADENOVIRAL GENE-TRANSFER"'

1. Immunoselection and adenoviral genetic modulation of human osteoprogenitors: in vivo bone formation on PLA scaffold

Author

Howard, Daniel, Partridge, Kris, Yang, Xuebin, Clarke, Nicholas M.P., Okubo, Yasunori, Bessho, Kazuhisa, Howdle, Steven M., Shakesheff, Kevin M., and Oreffo, Richard O.C.

Subjects
*BONES, *BONE marrow, *CELL separation
Abstract

The aim of this study was to examine the potential of immunoselected genetically modified human osteoprogenitors to form bone in vivo on porous PLA scaffolds. Human osteoprogenitors from bone marrow were selected using the antibody STRO-1 utilising a magnetically activated cell separation system. The STRO-1+ fraction isolated 7% of nucleated marrow cells and increased fibroblastic colony formation by 300% and alkaline phosphatase activity by 190% over unselected marrow cell cultures. To engineer bone tissue, STRO-1+ culture-expanded cells were transduced with AxCAOBMP-2, an adenovirus carrying the human BMP-2 gene, injected into diffusion chambers containing porous PLA scaffolds, and implanted in vivo. After 11 weeks the presence of bone mineral was observed by X-ray analysis and confirmed for mineral by von Kossa, as well as bone matrix composition by Sirius red staining, birefringence, and type I collagen immunohistochemistry. Bone formation in vivo indicates the potential of using immunoselected progenitor cells and ex vivo gene transfer with biodegradable scaffolds, for the development of protocols for the treatment of a wide variety of musculo-skeletal disorders. [Copyright &y& Elsevier]

Published
2002
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2. Adenoviral BMP-2 Gene Transfer in Mesenchymal Stem Cells: In Vitro and in Vivo Bone Formation on Biodegradable Polymer Scaffolds

Author

Partridge, Kris, Yang, Xuebin, Clarke, Nicholas M. P., Okubo, Yasunori, Bessho, Kazuhisa, Sebald, Walter, Howdle, Steven M., Shakesheff, Kevin M., and Oreffo, Richard O. C.

Subjects
*ADENOVIRUSES, *GENETIC transformation, *BONE marrow cells
Abstract

The aim of this study was to determine the feasibility of adenoviral gene transfer into primary human bone marrow osteoprogenitor cells in combination with biodegradeable scaffolds to tissue-engineer bone. Osteoprogenitors were infected with AxCAOBMP-2, a vector carrying the human BMP-2 gene. Alkaline phosphatase activity was induced in C2C12 cells following culture with conditioned media from BMP-2 expressing cells, confirming successful secretion of active BMP-2. Expression of alkaline phosphatase activity, type I collagen and mineralisation confirmed bone cell differentiation and maintenance of the osteoblast phenotype in extended culture for up to 6 weeks on PLGA porous scaffolds. In vivo implantation of adenoviral osteoprogenitor constructs on PLGA biodegradeable scaffolds, using diffusion chambers, also demonstrated bone cell differentiation and production of bone tissue. The maintenance of the osteoblast phenotype in extended culture and generation of mineralised 3-D scaffolds containing such constructs indicate the potential of such bone tissue engineering approaches in bone repair. [Copyright &y& Elsevier]

Published
2002
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3. Phenotype modulation of airway smooth muscle in asthma

Author

Thomas Trian, Jill R. Johnson, Oluwaseun O. Ojo, Sana Siddiqui, Rushita A. Bagchi, Varsha Kanabar, Christopher D. Pascoe, David Wright, Bart G. J. Dekkers, Shyamala Dakshinamurti, Janette K. Burgess, Molecular Pharmacology, Groningen Research Institute for Asthma and COPD (GRIAC), and Restoring Organ Function by Means of Regenerative Medicine (REGENERATE)

Subjects
Pulmonary and Respiratory Medicine, EXPRESSION, EXTRACELLULAR-MATRIX PROTEINS, Cell, Myocytes, Smooth Muscle, Synthetic response, Phenotypic plasticity, Biology, CELL-PROLIFERATION, C/EBP-ALPHA, CCAAT/ENHANCER-BINDING-PROTEIN, Cell Movement, Serum response factor, medicine, Myocyte, Animals, Humans, ADENOVIRAL GENE-TRANSFER, ALLERGIC-ASTHMA, Pharmacology (medical), Secretion, SIGNAL-REGULATED KINASE, SERUM RESPONSE FACTOR, Cell Proliferation, Cell growth, Biochemistry (medical), Contractile response, Muscle, Smooth, IN-VITRO, respiratory system, musculoskeletal system, Phenotype, Asthma, Cell biology, respiratory tract diseases, Airway smooth muscle, medicine.anatomical_structure, Cell culture, Immunology, Inflammation Mediators, Muscle Contraction
Abstract

The biological responses of airway smooth muscle (ASM) are diverse, in part due to ASM phenotype plasticity. ASM phenotype plasticity refers to the ability of ASM cells to change the degree of a variety of functions, including contractility, proliferation, migration and secretion of inflammatory mediators. This plasticity occurs due to intrinsic or acquired abnormalities in ASM cells, and these abnormalities or predisposition of the ASM cell may alter the ASM response and in some cases recapitulate disease hallmarks of asthma.These phenotypic changes are ultimately determined by multiple stimuli and occur due to alterations in the intricate balance or reversible state that maintains ASM cells in either a contractile or synthetic state, through processes termed maturation or modulation, respectively. To elucidate the role of ASM phenotype in disease states, numerous in vitro studies have suggested a phenotypic switch in ASM primary cell cultures as an explanation for the plethora of responses mediated by ASM cells. Moreover, there is overwhelming evidence suggesting that the immunomodulatory response of ASM is due to the acquisition of a synthetic phenotype; however, whether this degree of plasticity is present in vivo as opposed to cell culture-based models remains speculative. Nonetheless, this review will give an overall scope of ASM phenotypic markers, triggers of ASM phenotype modulation and novel therapeutic approaches to control ASM phenotype plasticity. (C) 2012 Elsevier Ltd. All rights reserved.

Published
2013

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