Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.413380
Title: Development and characterisation of 3D skeletal muscle constructs under defined mechanical regulation
Author: Cheema, Umber
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2005
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Abstract:
It has been shown that the IGF-I gene is spliced in response to mechanical signals producing forms of IGF-I which have different actions. To study the roles of environmental mechanical cues on gene programming and splicing in developing muscle, an in vitro 3D cell culture system was employed. C2C12 skeletal myoblasts were grown in 3D collagen cultures. The presence of this extracellular matrix component, the application of uniaxial strain (produced endogenously by the myoblasts) and a high concentration of cells was shown to enhance differentiation in these cultures. These differentiated myotube cultures were then subjected to different regimens of exogenous mechanical strain. IGF-IEa, which initiates the fusion of myoblasts to form myotubes, was found to be constitutively expressed in myoblasts and myotubes and its expression up-regulated by a single ramp stretch of one hour duration but reduced by repeated cyclical stretch. In contrast, MGF which is involved in the proliferation of mononucleated myoblasts, that are required for secondary myotube formation and to establish the muscle satellite (stem) cell pool, showed no significant constitutive expression in static cultures, but was up-regulated by a single ramp stretch and by cycling loading. The latter types of force simulate those generated in myoblasts by the first contractions of myotubes. These data indicate the importance of understanding the physiological signals that determine the ratios of splice variants of some growth factor/tissue factor genes in the early stages of development of skeletal muscle.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.413380  DOI: Not available
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