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Constricted migration modulates stem cell differentiation.

Lucas R Smith1,2,3, Jerome Irianto1, Yuntao Xia1

  • 1Molecular and Cell Biophysics Laboratory, University of Pennsylvania, Philadelphia, PA 19104.

Molecular Biology of the Cell
|June 13, 2019
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Summary
This summary is machine-generated.

Constricted cell migration damages DNA and impairs muscle regeneration by stressing nuclei. However, this process may enhance bone formation in mesenchymal stem cells (MSCs), showing tissue repair is context-dependent.

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Area of Science:

  • Cell Biology
  • Tissue Engineering
  • Regenerative Medicine

Background:

  • Tissue regeneration relies on stem cell proliferation, migration, and differentiation.
  • Dense tissues can constrict migrating cells, leading to nuclear stress.

Purpose of the Study:

  • To investigate the impact of constricted cell migration on nuclear integrity, DNA damage, and differentiation.
  • To explore the effects on myoblasts and mesenchymal stem cells (MSCs).

Main Methods:

  • Studied myoblastic cell types and human MSCs undergoing constricted migration in vitro.
  • Assessed nuclear rupture, DNA damage, cell cycle progression, and differentiation markers.
  • Utilized myosin II inhibition and analyzed localization of key proteins like MyoD and KU80.

Main Results:

  • Constricted migration caused nuclear rupture, DNA damage, and suppressed myoblast differentiation and muscle regeneration in vivo.
  • Mitosis and cell cycle were inhibited, suggesting a checkpoint activation.
  • Nuclear rupture mislocalized differentiation factors; however, MSC osteogenesis increased, relevant to bone and fibrotic tissue repair.

Conclusions:

  • Cellular mechanical stress during migration significantly impacts stem cell function and tissue repair outcomes.
  • Nuclear damage and protein mislocalization disrupt muscle regeneration.
  • The effect of pore curvature on stem cell behavior can modulate tissue repair, with potential implications for bone formation and fibrotic conditions.