ARUP; ISBN: 978-0-9562121-5-3 - CMBBE 2012 - Cardiff University

EFFECT OF OSCILATORY FLOW ON MORPHOGEN DYNAMICS OF
MESENCHYMAL STROMAL CELLS
1. ABSTRACT
A. Latypova 1 , M. Gortchacow 2 , A. Terrier 2 and D.P. Pioletti 3
Experiments have showed that mesenchymal stromal cells (MSCs) involved in the bone
healing process around orthopedic implants are sensitive to the flow. Nevertheless,
mechanism of how fluid flow influences MSCs differentiation - through flow-induced
shear stress, chemotransport, or both - is still unclear. It is well known that
differentiation starts when morphogens (ligands secreted by MSCs) bound to
transmembrane receptors form complexes, and thereby initiate transduction cascades.
Therefore we suggest that fluid flow can disturb ligands concentration profile providing
change in bound receptors number in comparison to its reference state (without fluid
flow) and regulating differentiation pathway. To test this hypothesis, we have developed
a numerical advection-diffusion-reaction model, which simulates a micro-fluidic
chamber with MCSs. In this paper, we analyze the effect of an oscillating laminar flow
on cells response, and more precisely the effect of its frequency. The model was
implemented in COMSOL. We found that cell response decreased when frequency
increased, which confirms experimental observations. As frequency increased, the state
of the MCSs was closer to a no-flow reference state. This result supports the importance
of chemo-transport contribution to cells response on fluid flow. Since bone-implant
interfacial flow is assumed to be oscillatory, regulated by activities of daily living such
as walking, we could propose an optimal activity level during bone healing phase
following surgery.
2.INTRODUCTION
Mesenchymal stromal cell (MSC) are multipotent stem cells that can differentiate into a
variety of cell types, such as osteoblasts, chondrocytes and adipocytes, therefore
providing normal organism development and maintenance [1]. The understanding of
MSC differentiation mechanisms has implication in developmental biology, in pathophysiology
aspect such as cancer, and osteointegration of implants. Two factors are
proposed to influence MSC differentiation: soluble growth factors and mechanical
stimulation.
Role of soluble growth factors have been clearly identified and demonstrated to be
involved in MSC differentiation [1]. For example, morphogens such as bone
morphogentic protein (BMP) or Wnt protein were shown to be central in the
differentiation of MSC into osteoblastic lineage [2, 3]. As the morphogen-induced
differentiation starts when ligand/receptor complexes are formed, a dynamic situation is
1
PhD student, Laboratory of Biomechanical Orthopedics, EPFL, Station 19, CH-1015, Lausanne,
Switzerland
2
PhD, Laboratory of Biomechanical Orthopedics, EPFL, Station 19, CH-1015, Lausanne, Switzerland
3
Assistant professor, Laboratory of Biomechanical Orthopedics, EPFL, Station 19, CH-1015, Lausanne,
Switzerland