A Flexible or Inflexible Fate?

Abstract

The specific factors in the local microenvironment that govern the differentiation of bone-marrow-derived mesenchymal stem cells (MSCs) into such disparate cell types as neurons, myoblasts, and osteoblasts remain incompletely understood (see Even-Ram et al. ). Noting that brain 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 determined by bis-acrylamide crosslinking 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) 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 lineage. A. J. Engler, S. Sen, H. L. Sweeney, D. E. Discher, Matrix elasticity directs stem cell lineage specification. Cell 126 , 677-689 (2006). [PubMed] S. Even-Ram, V. Artym, K. M. Yamada, Matrix control of stem cell fate. Cell 126 , 645-647 (2006). [PubMed]