TY - JOUR
T1 - Phenotype Transformation of Aortic Valve Interstitial Cells Due to Applied Shear Stresses Within a Microfluidic Chip
AU - Wang, Xinmei
AU - Lee, Joohyung
AU - Ali, Mir
AU - Kim, Jungkyu
AU - Lacerda, Carla M.R.
N1 - Publisher Copyright:
© 2017, Biomedical Engineering Society.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - Despite valvular heart diseases constituting a significant medical problem, the acquisition of information describing their pathophysiology remains difficult. Due to valvular size, role and location within the body, there is a need for in vitro systems that can recapitulate disease onset and progression. This study combines the development of an in vitro model and its application in the mechanical stimulation of valvular cell transformation. Specifically, porcine aortic valvular interstitial cells (PAVIC) were cultured on polydimethylsiloxane microfluidic devices with or without exposure to shear stresses. Mechanobiological responses of valvular interstitial cells were evaluated at shear stresses ranging from 0 to 4.26 dyn/cm2. When flow rates were higher than 0.78 dyn/cm2, cells elongated and aligned with the flow direction. In addition, we found that shear stress enhanced the formation of focal adhesions and up-regulated PAVIC transformation, assessed by increased expression of α-smooth muscle actin and transforming growth factor β. This study reveals a link between the action of shear forces, cell phenotype transformation and focal adhesion formation. This constitutes the first step towards the development of co-cultures (interstitial-endothelial cells) on organ-on-a-chip devices, which will enable studies of the signaling pathways regulating force-induced valvular degeneration in microtissues and potential discovery of valvular degeneration therapies.
AB - Despite valvular heart diseases constituting a significant medical problem, the acquisition of information describing their pathophysiology remains difficult. Due to valvular size, role and location within the body, there is a need for in vitro systems that can recapitulate disease onset and progression. This study combines the development of an in vitro model and its application in the mechanical stimulation of valvular cell transformation. Specifically, porcine aortic valvular interstitial cells (PAVIC) were cultured on polydimethylsiloxane microfluidic devices with or without exposure to shear stresses. Mechanobiological responses of valvular interstitial cells were evaluated at shear stresses ranging from 0 to 4.26 dyn/cm2. When flow rates were higher than 0.78 dyn/cm2, cells elongated and aligned with the flow direction. In addition, we found that shear stress enhanced the formation of focal adhesions and up-regulated PAVIC transformation, assessed by increased expression of α-smooth muscle actin and transforming growth factor β. This study reveals a link between the action of shear forces, cell phenotype transformation and focal adhesion formation. This constitutes the first step towards the development of co-cultures (interstitial-endothelial cells) on organ-on-a-chip devices, which will enable studies of the signaling pathways regulating force-induced valvular degeneration in microtissues and potential discovery of valvular degeneration therapies.
KW - Heart valve degeneration
KW - Mechanotransduction
KW - Microfluidic in vitro model
KW - Organ-on-a-chip
UR - http://www.scopus.com/inward/record.url?scp=85020494679&partnerID=8YFLogxK
U2 - 10.1007/s10439-017-1871-z
DO - 10.1007/s10439-017-1871-z
M3 - Article
C2 - 28620766
AN - SCOPUS:85020494679
VL - 45
SP - 2269
EP - 2280
JO - Annals of Biomedical Engineering
JF - Annals of Biomedical Engineering
SN - 0090-6964
IS - 10
ER -