Artificial Organs
29(3):264–267, Blackwell Publishing, Inc.
© 2005 International Center for Artificial Organs and Transplantation
264
Blackwell Science, LtdOxford, UKAORArtificial Organs0160-564X2005 International Society for Artificial OrgansMarch 2005293264267Miscellaneous THOUGHTS AND PROGRESSTHOUGHTS AND PROGRESS
Received March 2004; revised August 2004.
Address correspondence and reprint requests to Dr. Igor M.
Sauer, Visceral and Transplantation Surgery, Experimental
Surgery and Regenerative Medicine, Charité, Campus Virchow,
Augustenburger Platz 1, 13353 Berlin, Germany. E-mail:
igor.sauer@charite.de
Thoughts and Progress
The SlideReactor—A Simple Hollow Fiber
Based Bioreactor Suitable for
Light Microscopy
*Igor M. Sauer, *Ruth Schwartlander,
*Jochen Schmid, *Ekaterina Efimova,
*Florian W.R. Vondran, *Daniel Kehr, *Gesine Pless,
*Antonio Spinelli, †Börries Brandenburg,
†Eberhardt Hildt, and *Peter Neuhaus *Visceral and
Transplantation Surgery, Experimental Surgery and
Regenerative Medicine Charité—Campus Virchow
Universitätsmedizin Berlin; †Robert Koch Institute,
Molecular Virology NG1, Berlin, Germany
Abstract: Most bioartificial liver support systems are
based on hollow fiber capillaries within modified dialysis
cartridges or more sophisticated bioreactor constructions.
Due to their design microscopic follow-up of reorganiza-
tion and growth of tissue between the hollow fibers is
not possible. The SlideReactor is a simple hollow fiber
based bioreactor construction suitable for light microscopy
and time-lapse video observation. The SlideReactor offers
a cell compartment separated from a medium inflow and
outflow compartment. Cell compartment access ports
enable easy filling of the cell compartment with cell sus-
pension, as well as fixation of the tissue. For more complex
procedures or full access to all the cells, the bioreactor can
be opened easily by cutting the silicone seal with a scalpel.
Due to its simple design and the utilization of standard
materials, it could serve as a suitable, cost-efficient tool to
evaluate the behavior of cells cultured between hollow
fiber capillaries. The paper describes the production pro-
cess: similar to open source projects in software engineer-
ing, we would like to propose the concept as an open
platform to anyone interested in hollow fiber based cell
culture. Key Words: Bioreactor—Microscopy—Hollow
fibers—Time-lapse video microscopy—Cell culture.
Conventional culture techniques lead to an alter-
ation in the environmental conditions of liver cells
in comparison to their in vivo situation. Electron
microscopy investigations have demonstrated that
major differences in the ultrastructure of hepatocytes
can be observed when cultured, using monolayer
techniques. Important findings are the endocytosis of
the junctional complexes with secondary effects
on the orientation of the cytoskeleton and cell
organelles (1). If a culture model could support high
cell densities (2), as well as a free three-dimensional
cell rearrangement, a more physiological microenvi-
ronment of hepatocytes could be established. Cell-
to-cell aggregation would enable the reconstruction
of functional complexes, as well as the reorientation
of the cytoskeleton and cell organelles in vitro (3).
Furthermore, a liver tissue-like formation of paren-
chymal and nonparenchymal cells is thought to sup-
port cellular orientation and differentiated function.
A culture technique in which the different cell
populations can reorganize themselves into three-
dimensional structures may result in a hepatocyte
microenvironment similar to the physiological situa-
tion along the liver sinusoids.
An early approach to cultivate an appropriate
quantity of cells under conditions acceptable for cell
culture and clinical use, was the use of hollow fiber
capillaries within modified dialysis and plasma sepa-
ration cartridges. In addition to cell immobilization,
capillary membranes allow: gas exchange, substrate
supply, waste removal, and easy interface with the
blood or plasma circuit of the patient during clinical
application. Modified dialysis cartridges or more
sophisticated bioreactors enable the clinical use of
liver cells. These systems consist of a collection of
hollow fiber capillaries through which the patient’s
blood or plasma is pumped (4). Within the Extra-
corporeal Liver Assist Device (ELAD) cells are
inoculated into the extracapillary space (5). An-
other design (Academisch-Medisch-Centrum Bio-
Artificial Liver, AMC-BAL) by Chamuleau and
coworkers incorporates a spirally wound polyester
matrix sheet which includes an integral hollow-fiber
compartment for oxygenation (6). The CellModule
uses independently perfused but interwoven hollow
fiber membranes to create a three-dimensional frame-
work over which self-assembling hepatocyte aggre-
gates are distributed (7,8). By using hollow fiber
capillaries these bioreactors imitate the conditions
in the natural liver where each hepatocyte is in close
contact with the intrahepatic blood vessels.
Since these systems are not suitable for direct anal-
ysis of the reorganization or growth of tissue between