Stiffness Gradients Mimicking In Vivo Tissue Variation Regulate Mesenchymal Stem Cell Fate

PLoS One

Justin R. Tse¹  Adam J. Engler¹ 

[1] Department of Bioengineering, University of California San Diego, La Jolla, California, United States of America

关键词: Gels;    Mesenchymal stem cells;    Stiffness;    Tubulins;    Collagens;    Cell differentiation;    Cell staining;    Myoblasts;   

DOI  :  10.1371/journal.pone.0015978

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Mesenchymal stem cell (MSC) differentiation is regulated in part by tissue stiffness, yet MSCs can often encounter stiffness gradients within tissues caused by pathological, e.g., myocardial infarction ∼8.7±1.5 kPa/mm, or normal tissue variation, e.g., myocardium ∼0.6±0.9 kPa/mm; since migration predominantly occurs through physiological rather than pathological gradients, it is not clear whether MSC differentiate or migrate first. MSCs cultured up to 21 days on a hydrogel containing a physiological gradient of 1.0±0.1 kPa/mm undergo directed migration, or durotaxis, up stiffness gradients rather than remain stationary. Temporal assessment of morphology and differentiation markers indicates that MSCs migrate to stiffer matrix and then differentiate into a more contractile myogenic phenotype. In those cells migrating from soft to stiff regions however, phenotype is not completely determined by the stiff hydrogel as some cells retain expression of a neural marker. These data may indicate that stiffness variation, not just stiffness alone, can be an important regulator of MSC behavior.

【 授权许可】

CC BY