Department of Bioengineering, University of California San Diego, La Jolla, California, United States of America.
PLoS One. 2011 Jan 5;6(1):e15978. doi: 10.1371/journal.pone.0015978.
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.
间充质干细胞 (MSC) 的分化部分受组织硬度调节，但 MSCs 通常可在组织中遇到由病理变化（例如心肌梗塞约 8.7±1.5kPa/mm）或正常组织变化（例如心肌约 0.6±0.9kPa/mm）引起的硬度梯度；由于迁移主要通过生理梯度而不是病理梯度发生，因此尚不清楚 MSC 是先分化还是先迁移。在含有 1.0±0.1kPa/mm 生理梯度的水凝胶上培养长达 21 天的 MSC 经历定向迁移，或趋硬性迁移，向上硬度梯度迁移而不是保持静止。对形态和分化标志物的时间评估表明，MSC 迁移到较硬的基质中，然后分化为更具收缩性的肌原性表型。然而，在从软到硬区域迁移的细胞中，表型并非完全由硬水凝胶决定，因为一些细胞保留了神经标志物的表达。这些数据可能表明，不仅是刚度，刚度变化也可以是 MSC 行为的重要调节剂。
