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Controlling Cell Density by Micropatterning Regulates Smad Signalling and Mesendoderm Differentiation of Human Embryonic Stem Cells

Human embryonic stem cells (hESC) present a potentially unlimited supply of hematopoietic progenitors for cell-based therapies. However, current protocols for generating these progenitors typically also generate undesired cell types due to imprecise control of the hESC microenvironment and poor understanding of the signalling networks regulating mesoderm differentiation (the germ layer from which hematopoietic cells emerge). This report demonstrates that activation of the downstream effectors of Activin/Nodal and bone morphogenetic protein (BMP) signalling (Smad2 (composite of Sma (smaller) and Mad (mothers against decapentaplegic) and Smad1, respectively) are both required for mesoderm differentiation. It is further shown that microcontact printing-mediated control of hESC colony size creates local microenvironments that guide differentiation, via a Smad1-dependent mechanism, preferentially towards the mesoderm lineage. These findings demonstrate the need for precise control of the microenvironment in order to effectively guide hESC differentiation to produce specific cell types for potential therapeutic applications.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/17192
Date24 February 2009
CreatorsLee, Lawrence
ContributorsZandstra, Peter W.
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis
Format3162251 bytes, application/pdf

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