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DEPARTAMENTO DE CIÊNCIAS DA VIDA ... - Estudo Geral

DEPARTAMENTO DE CIÊNCIAS DA VIDA ... - Estudo Geral

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viii<br />

Table of contents<br />

Acknowledgements<br />

i<br />

Abstract<br />

iii<br />

Resumo<br />

v<br />

Table of contents<br />

viii<br />

List of figures<br />

xi<br />

List of tables<br />

List of abbreviations<br />

Chapter I 1<br />

I – Introduction 3<br />

I.1. Mesenchymal stem cells (MSCs) 3<br />

I.1.1 - Sources of MSCs 3<br />

I.1.2 -In vitro characterization of MSCs 4<br />

I.1.2.1 - Immunophenotype 5<br />

I.1.2.2 - CFU-F and proliferation capacity 5<br />

I.1.2.3 -Multilineage differentiation capacity 5<br />

I.2. - Mechanotransduction and its implications in cellular fate 6<br />

I.2.1 -Mechanotransduction and mechanosensors 9<br />

I.2.2 -Extracellular matrix and integrin-based mechanotransduction<br />

Mechanisms 11<br />

I.2.2.1 -Mechanisms of Rigidity Sensing 11<br />

I.2.3 -Mechanotransduction and Stem Cells 15<br />

I.2.3.1 - Mechanotransduction and MSCs differentiation 15<br />

I.2.3.1.1-Stiffness effect on Neuronal and Glial<br />

differentiation 19<br />

I.2.3.2-Manipulation and measurement of cellular forces<br />

in MSCs 21<br />

I.3 - Project rationale and experimental approach 24<br />

I.3.1 -Typical MSCs Isolation 24<br />

I.3.2 -Durotaxis, Tissue Elasticity and MSCs “memory” 24<br />

I.3.3 - Effects of the stiffness on the MSCs stemness genes 27

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