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A B C
D
E
Figure 2. Tissue reconstruction as a precondition for spatial-temporal modelling. Confocal Z-scans
(A) are used to reconstruct the microvessel network (B) and small tissue blocks (C). D-E: Several
segments are composed to reconstruct entire liver lobules (from: Hoehme et al., 2010).
modifications on tissue architecture of
mice (Braeuning et al., 2010).
Prediction of a Novel Key
Mechanism of Liver Regeneration
One of the achievements of the novel
approach is that tissue architecture (e.g.,
calculated as the contact surface between
hepatocytes and sinusoids) can be
analysed by quantitative measures. This
provides the opportunity to (i) simulate
the scenario after tissue damage and (ii)
experimentally determine the situation to
analyse if the experiment and the model
prediction are in agreement. Interestingly,
experimental data and simulation
were only in agreement when a so far
unrecognised mechanism was assumed,
which we named “hepatocyte sinusoidal
alignment” (HSA). HSA means that during
hepatocyte division the orientation of the
mitotic spindle is initially random (Figure
3A). However, after mitosis the daughter
cells rapidly realign in the direction of
the closest sinusoid. This mechanism
was predicted by the model and could
later be validated by extensive tissue
reconstructions, where an automated
algorithm measured the angles between
the lines through the centre of two
daughter hepatocytes and the orientation
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AXLR8-2 WORKSHOP REPORT
Progress Report 2011 & AXLR8-2 Workshop Report