Geometric cues for directing the differentiation of mesenchymal stem cells

Kristopher A. Kilian, Branimir Bugarija, Bruce T. Lahn, Milan Mrksich*

*Corresponding author for this work

Research output: Contribution to journalArticle

1159 Scopus citations

Abstract

Significant efforts have been directed to understanding the factors that influence the lineage commitment of stem cells. This paper demonstrates that cell shape, independent of soluble factors, has a strong influence on the differentiation of human mesenchymal stem cells (MSCs) from bone marrow. When exposed to competing soluble differentiation signals, cells cultured in rectangles with increasing aspect ratio and in shapes with pentagonal symmetry but with different subcellular curvature - and with each occupying the same area - display different adipogenesis and osteogenesis profiles. The results reveal that geometric features that increase actomyosin contractility promote osteogenesis and are consistent with in vivo characteristics of the microenvironment of the differentiated cells. Cytoskeletal-disrupting pharmacological agents modulate shape-based trends in lineage commitment verifying the critical role of focal adhesion and myosin-generated contractility during differentiation. Microarray analysis and pathway inhibition studies suggest that contractile cells promote osteogenesis by enhancing c-Jun N-terminal kinase (JNK) and extracellular related kinase (ERK1/2) activation in conjunction with elevated winglesstype (Wnt) signaling. Taken together, this work points to the role that geometric shape cues can play in orchestrating the mechano-chemical signals and paracrine/autocrine factors that can direct MSCs to appropriate fates.

Original languageEnglish (US)
Pages (from-to)4872-4877
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number11
DOIs
StatePublished - Mar 16 2010

Keywords

  • Cytoskeleton
  • Microcontact printing
  • Microenvironment
  • Wnt signaling

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Geometric cues for directing the differentiation of mesenchymal stem cells'. Together they form a unique fingerprint.

  • Cite this