Cell News 01/2017
29
3D cell biology meets synthetic materials:
Microvascular network formation by endothelial
cells in ECM-free hydrogels
Ulrich Blache, Ai Hsin, Martin Ehrbar
Presenting author: Ulrich Blache
ETH Zurich, Institut for Biomechanics, University of Zurich,
Department of Obstetrics
The extra cellular matrix (ECM) is the physiological material
surrounding cells in tissues. Components derived from the nat-
ural ECM such as fibrinogen, collagen type 1 or collagen type
4 (matrigel) are widely used as 3D hydrogel scaffolds in cell
biology. However, such natural ECM components show batch-
to-batch variability, are difficult to modify towards customized
requirements and trigger cellular responses by itself. These
limitations can be overcome by using synthetic materials that
mimic the natural ECM and are formed under fully controlled
conditions. Here, we introduce synthetic poly(ethylene glycol)
(PEG) hydrogels as 3D cell culture platforms to study angio-
genesis and microvascular network formation. Human endo-
thelial cells and human mesenchymal stem cells (MSCs) are 3D
encapsulated in PEG hydrogels and the resulting co-cultures
are analyzed by various microscopy techniques. We show that
in synthetic environments MSCs and the endogenously depos-
ited ECM enable endothelial cells to form stable, lumenized
and 3D-aligned microvascular tubes that are surrounded by
supporting cells and a dense ECM layer.
We envision synthetic hydrogels to become powerful tools in
cell biology to e.g. address the role of the endogenous ECM in
cell biological processes such as but not limited to the forma-
tion of the microvasculature.
OTHER TOPICS
It is not who you are but what you do –
stem cell micromanagment by the niche
Puretskaia Olga, Albert Eugene, Terekhanova Nadezhda
Presenting author: Christian Bökel
CRTD, TU Dresden, Fetscherstr. 105, 01307 Dresden
Niches are typically characterized as signalling microenvi-
ronments that allow stem cells to maintain their fate. This
definition traditionally implies the integration of multiple
niche signals towards a binary decision between stemness
and differentiation. However, recent observations in multiple
organisms have challenged this textbook model. For example, it
cannot easily account for stem cell / niche systems exhibiting
high plasticity such as in the mammalian intestine, or involving
both dedifferentiation and lineage memory as exemplified by
zebrafish fin regeneration.
We have studied the role of the transcriptional regulator Zfh1,
a shared target of Hedgehog and Jak/STAT niche signalling,
for the proliferation of the somatic cyst stem cells (CySCs) in
the Drosophila testis. We found that Zfh1 binds and down-
regulates salvador (sav) and kibra, two tumour suppressors
of the Hippo/Wts/Yki pathway. Yki activation and somatic
proliferation are thereby restricted to the Zfh1 positive CySCs.
Experimental activation of Hh or Yki signalling is sufficient for
CySC overproliferation, but has no effect on the differentiation
propensity of the affected cells. These niche signals therefore
do not contribute to an overall fate decision that subsequently
governs CySC behaviour. In addition, preliminary experiments
suggest that also the competitive behaviour of stem cells and
their Warburg-like, glycolytically biased metabolism are caused
by direct instructions from the niche.
Generalizing from these observations we would like to suggest
that the true function of the niche is not to aid resident stem
cells in choosing between stemness and proliferation, but to
directly instruct competent cells to execute stem cell specific
behaviours. We would like to propose the term "micromanage-
ment" for this mode of niche mediated stem cell regulation.
