Fluid-flow-induced mesenchymal stem cell migration

role of focal adhesion kinase and RhoA kinase sensors

Brandon D. Riehl, Jeong Soon Lee, Ligyeom Ha, Jung Y Lim

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The study of mesenchymal stem cell (MSC) migration under flow conditions with investigation of the underlying molecular mechanism could lead to a better understanding and outcome in stem-cell-based cell therapy and regenerative medicine. We used peer-reviewed open source software to develop methods for efficiently and accurately tracking, measuring and processing cell migration as well as morphology. Using these tools, we investigated MSC migration under flow-induced shear and tested the molecular mechanism with stable knockdown of focal adhesion kinase (FAK) and RhoA kinase (ROCK). Under steady flow, MSCs migrated following the flow direction in a shear stress magnitude-dependent manner, as assessed by root mean square displacement and mean square displacement, motility coefficient and confinement ratio. Silencing FAK in MSCs suppressed morphology adaptation capability and reduced cellular motility for both static and flow conditions. Interestingly, ROCK silencing significantly increased migration tendency especially under flow. Blocking ROCK, which is known to reduce cytoskeletal tension, may lower the resistance to skeletal remodelling during the flow-induced migration. Our data thus propose a potentially differential role of focal adhesion and cytoskeletal tension signalling elements in MSC migration under flow shear.

Original languageEnglish (US)
Number of pages1
JournalJournal of the Royal Society, Interface / the Royal Society
Volume12
Issue number104
DOIs
StatePublished - Mar 6 2015

Fingerprint

Focal Adhesion Protein-Tyrosine Kinases
Stem cells
Mesenchymal Stromal Cells
Cell Movement
Flow of fluids
Phosphotransferases
Adhesion
Sensors
Focal Adhesions
Regenerative Medicine
Steady flow
Shear flow
Cell- and Tissue-Based Therapy
Shear stress
Stem Cells
Software
Processing

Keywords

  • RhoA kinase
  • fluid shear
  • focal adhesion kinase
  • stem cell migration
  • time lapse

ASJC Scopus subject areas

  • Biotechnology
  • Biophysics
  • Bioengineering
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering

Cite this

Fluid-flow-induced mesenchymal stem cell migration : role of focal adhesion kinase and RhoA kinase sensors. / Riehl, Brandon D.; Lee, Jeong Soon; Ha, Ligyeom; Lim, Jung Y.

In: Journal of the Royal Society, Interface / the Royal Society, Vol. 12, No. 104, 06.03.2015.

Research output: Contribution to journalArticle

@article{a73c6e53f87348aaa19c504e802686f1,
title = "Fluid-flow-induced mesenchymal stem cell migration: role of focal adhesion kinase and RhoA kinase sensors",
abstract = "The study of mesenchymal stem cell (MSC) migration under flow conditions with investigation of the underlying molecular mechanism could lead to a better understanding and outcome in stem-cell-based cell therapy and regenerative medicine. We used peer-reviewed open source software to develop methods for efficiently and accurately tracking, measuring and processing cell migration as well as morphology. Using these tools, we investigated MSC migration under flow-induced shear and tested the molecular mechanism with stable knockdown of focal adhesion kinase (FAK) and RhoA kinase (ROCK). Under steady flow, MSCs migrated following the flow direction in a shear stress magnitude-dependent manner, as assessed by root mean square displacement and mean square displacement, motility coefficient and confinement ratio. Silencing FAK in MSCs suppressed morphology adaptation capability and reduced cellular motility for both static and flow conditions. Interestingly, ROCK silencing significantly increased migration tendency especially under flow. Blocking ROCK, which is known to reduce cytoskeletal tension, may lower the resistance to skeletal remodelling during the flow-induced migration. Our data thus propose a potentially differential role of focal adhesion and cytoskeletal tension signalling elements in MSC migration under flow shear.",
keywords = "RhoA kinase, fluid shear, focal adhesion kinase, stem cell migration, time lapse",
author = "Riehl, {Brandon D.} and Lee, {Jeong Soon} and Ligyeom Ha and Lim, {Jung Y}",
year = "2015",
month = "3",
day = "6",
doi = "10.1098/rsif.2014.1351",
language = "English (US)",
volume = "12",
journal = "Journal of the Royal Society Interface",
issn = "1742-5689",
publisher = "Royal Society of London",
number = "104",

}

TY - JOUR

T1 - Fluid-flow-induced mesenchymal stem cell migration

T2 - role of focal adhesion kinase and RhoA kinase sensors

AU - Riehl, Brandon D.

AU - Lee, Jeong Soon

AU - Ha, Ligyeom

AU - Lim, Jung Y

PY - 2015/3/6

Y1 - 2015/3/6

N2 - The study of mesenchymal stem cell (MSC) migration under flow conditions with investigation of the underlying molecular mechanism could lead to a better understanding and outcome in stem-cell-based cell therapy and regenerative medicine. We used peer-reviewed open source software to develop methods for efficiently and accurately tracking, measuring and processing cell migration as well as morphology. Using these tools, we investigated MSC migration under flow-induced shear and tested the molecular mechanism with stable knockdown of focal adhesion kinase (FAK) and RhoA kinase (ROCK). Under steady flow, MSCs migrated following the flow direction in a shear stress magnitude-dependent manner, as assessed by root mean square displacement and mean square displacement, motility coefficient and confinement ratio. Silencing FAK in MSCs suppressed morphology adaptation capability and reduced cellular motility for both static and flow conditions. Interestingly, ROCK silencing significantly increased migration tendency especially under flow. Blocking ROCK, which is known to reduce cytoskeletal tension, may lower the resistance to skeletal remodelling during the flow-induced migration. Our data thus propose a potentially differential role of focal adhesion and cytoskeletal tension signalling elements in MSC migration under flow shear.

AB - The study of mesenchymal stem cell (MSC) migration under flow conditions with investigation of the underlying molecular mechanism could lead to a better understanding and outcome in stem-cell-based cell therapy and regenerative medicine. We used peer-reviewed open source software to develop methods for efficiently and accurately tracking, measuring and processing cell migration as well as morphology. Using these tools, we investigated MSC migration under flow-induced shear and tested the molecular mechanism with stable knockdown of focal adhesion kinase (FAK) and RhoA kinase (ROCK). Under steady flow, MSCs migrated following the flow direction in a shear stress magnitude-dependent manner, as assessed by root mean square displacement and mean square displacement, motility coefficient and confinement ratio. Silencing FAK in MSCs suppressed morphology adaptation capability and reduced cellular motility for both static and flow conditions. Interestingly, ROCK silencing significantly increased migration tendency especially under flow. Blocking ROCK, which is known to reduce cytoskeletal tension, may lower the resistance to skeletal remodelling during the flow-induced migration. Our data thus propose a potentially differential role of focal adhesion and cytoskeletal tension signalling elements in MSC migration under flow shear.

KW - RhoA kinase

KW - fluid shear

KW - focal adhesion kinase

KW - stem cell migration

KW - time lapse

UR - http://www.scopus.com/inward/record.url?scp=84923247857&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923247857&partnerID=8YFLogxK

U2 - 10.1098/rsif.2014.1351

DO - 10.1098/rsif.2014.1351

M3 - Article

VL - 12

JO - Journal of the Royal Society Interface

JF - Journal of the Royal Society Interface

SN - 1742-5689

IS - 104

ER -