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

it has been shown how the effect of acidic pH (due to lactate accumulation) can be
detrimental to cell viability (Shirazi-Adl et al., 2010; Horner and Urban, 2001). Also,
glucose has been underlined as the most relevant nutrient affecting cell viability: Horner
and Urban (2001) have found that cell concentration in a diffusion chamber decayed
exponentially over time below critical glucose concentration and pH values.
Accordingly, cell viability criteria in a metabolic transport IVD FE model have been
introduced (Shirazi-Adl et al., 2010; Jackson et al., 2011; Galbusera et al., 2011).
However, the effect of mechanical loading over time has not been considered for a
realistic geometrical 3D model. Thus, our aim was to close this gap and determine
whether tissue deformation effects on metabolic transport would affect cell death within
the IVD.
3. METHODS
A coupled IVD FE mechano-transport model (Malandrino et al., 2011) was used. This
model, in particular, included a system of inter-related and in-vitro-derived (Bibby et
al., 2005) metabolic reactions:
.
.
.
.. [1]
exp2.47 0.93 0.16 0.0058
[2]
[3]
7.4 0.09 [4]
for oxygen, lactate, glucose and pH respectively. , were the oxygen and lactate
concentrations, respectively. Porosity and cell densities were referred
specifically to each IVD subtissue (Malandrino et al., 2011). Such model was modified
to include pH- and glucose-dependent cell viability criteria. Cell viability was
considered by modifying the cell density over time, depending on the glucose and
pH levels predicted. Based on the experimental results of Horner and Urban (2001), cell
death rates were represented by exponential functions of the type:
, exp
where the death rate constants are i = 9.28×10 −6 s -1 for i = glucose and i = 3.43×10 −6 s -1
for i = pH. The exponential decays were assumed to start when glucose and pH felt below
two critical values.
Such “threshold” values that initiated cell death were adjusted to reproduce realistically
the temporal and spatial in vitro viability curves as a function of cell density determined
in the above-cited experiment (Horner and Urban, 2001): A 26 mm width diffusion
chamber - filled with cells embedded in 1% agarose gel - was simulated according to
experimental tests on bovine nucleus cell viability (Horner and Urban, 2001). Oxygen,
lactate and glucose diffusivities accounted for gel porosity. Only half of a thin slice was
reproduced due to chamber geometry. Initial conditions were applied throughout the
chamber for the three metabolites to reproduce the experiment: an initial pH of 7.4 (i.e.