How Soft or Stiff Substrates Direct Stem Cell Differentiation

Mechanical signals point mesenchymal stem cells down a particular differentiation path, but not all cells follow the lead.

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Mesenchymal stem cells (MSCs) hold a lot of potential. They have the capacity to differentiate into bone and cartilage as well as muscle and fat. They are also critical to regenerating tissues, but how they go from stem cell to fat cell or bone cell is not completely understood.

Now, researchers revealed that the stiffness of the environment affects the fate of MSCs via changes in expression of a gene that regulates myosin contractility called tropomyosin-1 (TPM1). The findings demonstrated how extracellular clues inform stem cell responses in tissue regeneration, and add another clue to what drives heterogenous responses to mechanical cues.

The mechanical environment—how elastic the underlying substance is—influences what type of cells MSCs go on to become. Less elastic, stiff substrates promote differentiation into bone, while soft substrates favor fat. In the lab, researchers mimic the mechanical environment by culturing cells on hydrogel matrices that have measured elasticities. ...

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  • Roni Dengler, PhD

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