A Flexible Fate?

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Science  08 Sep 2006:
Vol. 313, Issue 5792, pp. 1365
DOI: 10.1126/science.313.5792.1365c

Specific factors in the local microenvironment govern the differentiation of bone marrow-derived mesenchymal stem cells (MSCs) into disparate cell types such as neurons, myoblasts, and osteoblasts, yet remain incompletely understood. Noting that brain tissue is much softer than muscle, which in turn is softer than collagenous bone, Engler et al. cultured naïve human MSCs on collagen-coated polyacrylamide gels in which elasticity was varied via the extent of bis-acrylamide crosslinking in order to investigate the role of matrix elasticity in lineage specification. The morphology, transcriptional profile, and expression of marker proteins of MSCs grown for a week on soft gels (mimicking brain tissue) resembled those of cultured neurons; MSCs grown on gels that mimicked the elasticity of striated muscle resembled myoblasts; and MSCs grown on gels that mimicked young uncalcified bone resembled osteoblasts. During the first week in culture, exposure to soluble factors known to promote myogenic or osteoblastic differentiation influenced lineage, leading to a mixed MSC phenotype. After 3 weeks in culture, however, MSCs remained committed to the matrix-derived lineage. Pharmacological analysis indicated that nonmuscle myosin II was required for lineage specification in response to matrix elasticity but not in response to soluble factors. Thus, the data suggest that matrix elasticity plays an important role in specifying MSC lineages. — EMA

Cell 126, 677 (2006).

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