Table Of ContentZbigniew Brzozka
Elzbieta Jastrzebska
Editors
Cardiac
Cell Culture
Technologies
Microfluidic and On-Chip Systems
Cardiac Cell Culture Technologies
Zbigniew Brzozka Elzbieta Jastrzebska
(cid:129)
Editors
Cardiac Cell Culture
Technologies
fl
Micro uidic and On-Chip Systems
123
Editors
Zbigniew Brzozka Elzbieta Jastrzebska
TheChair of Medical Biotechnology, TheChair of Medical Biotechnology,
Faculty ofChemistry Faculty ofChemistry
Warsaw University of Technology Warsaw University of Technology
Warsaw Warsaw
Poland Poland
ISBN978-3-319-70684-9 ISBN978-3-319-70685-6 (eBook)
https://doi.org/10.1007/978-3-319-70685-6
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I dedicate this book to my husband Mariusz,
for his understanding, boundless faith and
endless support…
Ela
Preface
Nowadays, one of the main branches of microfluidic development is cell engi-
neering. A number of the devices for the cell cultivation, Organ-on-a-chip, lysis,
single-cellanalysis,andcell-basedtoxicitytestsarebeingreported.Avarietyofthe
structuresthatcanbecreatedleadstoobtainingthedevicesmorecloselymimicking
the in vivo environment than classic cell culture. The microfluidic devices can
mimic the in vivo environment at various levels of its organization. It is expected
that research on microfluidic in vivo-like systems will effect in the evaluation of
methods that can replace animals in different fields of biomedical research.
Theapplicationofthemicrofluidicsystemscreatesapossibilitytorevolutionize
the methods applied in the cell biology research. Compatibility of the microchan-
nelstodimensionsofthecellsaswellastheabilitytocontrolparametersofthecell
microenvironment makes them an attractive tool for biological research. Cells and
their internal components have physical dimensions of microns so tools developed
with a microscale technology are invaluable and well suited for manipulation,
testing, and probing in microfluidic environment. Typical single processes as
growth,treatment,selection,lysis,separation,andanalysisaresuccessfullyrealized
inthemicrodimensionalsystems.TheLab-on-a-chipdeviceshaveagreatpotential
for improving sensitivity and complexity of experiments, where studies of cellular
growth and responses to external factors are conducted. The analytical devices
integrated with cell culture create a possibility for continuous monitoring of cell
behavior and biochemical processes as well. The usage of microscale analytical
systems would have a great impact on cell biology knowledge as microfluidic
devices have potential to improve the sensitivity and complexity of cellular
experiments.
The heart is one of the most important organs and performs a principal task in
the organism providing a blood through the vascular bed. Since cardiovascular
diseases(CVDs)areknowntobethemaincauseofmortalityinhumans,thereisa
huge interest in development of novel therapies for myocardial dysfunction. There
areanumberofproposedapproaches;however,abighopehasbeenplacedinstem
cell therapies.
vii
viii Preface
Chapter 1 is an overview of basics of the microfluidic systems for cellular
application, presenting important parameters of the microdevices, which have the
greatest impact on the cell behavior.
The main advantage tousing themicrosystemsis their ability to imitate invivo
conditionswhicharemissinginstaticmacroscalecellcultures.Inthenextchapter,
the materials which find applications in Lab-on-a-chip devices for cellomics, their
properties, microfabrication techniques, and examples from the literature were
described.
Organ-on-a-chipsystemsarenovelplatforms,whichimitatethekeyfunctionsof
a living organ, including specific microarchitectures, cell-cell and tissue-tissue
interactions, and extracellular communication. Microtechnology offers the possi-
bilityofcreatingmorecomplex,multi-organplatformsknownasBody-on-a-chipor
Human-on-a-chip. Such integration allows to conduct research on inter-tissue and
inter-organinteractionsaswellashumanmetabolismsimulation,whichplaysakey
role in studies on toxic and dose-related effects of novel therapies.
The next two chapters introduce two crucial application fields of this volume:
characteristics and engineering of stem cells and reconstruction attempts of heart,
the most “mystic” of human organs.
Stem cells widely used in the studies aiming to understand and also control
differentiation of various cell types as well as to design the therapeutic strategies
allowing to treat various degenerative diseases and to regenerate damaged tissues
and organs. Current review focuses on the selected studies aiming at their efficient
derivation and application in cellular therapies.
Wesummarizerecentadvancesintherapiesoftheheartandmethodsthatcould
be used to enhance their efficacy in clinical application.
Heart-on-a-chip systems are specific types of Organ-on-a-chip systems. The
aim of the fabrication of such systems is to develop an in vivo-like cardiac model,
in which the investigation of cardiac cell processes, as well as the elaboration of
new therapies for heart failure, will be possible.
Based on the properly designed microsystems, it is possible to perform rapid
drug screening and analysis of the effects of electrical stimulation. Thanks to this,
newmechanismsandcardiaccellfunctionscanbediscoveredandcanconsequently
be useful in regenerative medicine.
In the last chapter, we present cardiac cell culture microtechnologies based on
stem cells—the microsystems utilized for stem cells (SC) differentiation into car-
diomyocytes (CMs). Various types of SC differentiation performed in
Lab-on-a-Chipsystemsarepresentedinthischapter,includingcardiogenesisusing
biochemical, physical, and mechanical stimulations. Finally, we summarize the
researchfocusedonheartregenerationusingLab-on-a-chipsystemsandweoutline
future perspectives for the microsystems usage for SC differentiation into CMs.
The chapters of this volume were written by well-recognized experts in stem
cellsandtheirapplicationsintherapies,inheartdiseases,andtheirtherapiesbased
on stem cells. Some of the chapters were written by our research team long-term
expertiseinLab-on-a-Chiptechnologyorrelatedareas.Itwasimportantforusthat
each chapter gives an overview of the state of the art in the corresponding field.
Preface ix
This was achieved by including a relevant number of references, pointing out a
reader where further information can be found, especially in such an interdisci-
plinaryfieldasLab-on-a-Chiptechnology.Therefore,wehopethatthereadermay
find the extensive and up-to-date literature lists at the end of the chapters.
Warsaw, Poland Zbigniew Brzozka
Elzbieta Jastrzebska
Acknowledgements
This work was mainly realized with the frame of project LIDER
No. LIDER/026/573/L-4/12/NCBR/2013.
This work was realized with the frame of project SONATA 5 program
No. UMO-2013/09/D/ST5/03887.
This work was financially supported by a frame of OPUS 11 program
No. UMO-2016/21/B/ST5/01774 and Warsaw University of Technology.
Authors would like to acknowledge a financial support from the following
projects: National Centre for Research and Development, Grant
No. STRATEGMED1/233624/5/NCBR/2014 and Grant No. PBS3/A7/27/2015;
National Science Centre, Grant No. 2014/13/B/NZ3/04646.
DuringpreparationofthischapterKAwassupportedbygrantfromtheNational
Science Centre (NCN)—Grant No. 2012/05/D/NZ3/02081; EB was supported by
budget funds fromtheNationalCenter for Research andDevelopment (NCBiR)—
Grant No. STRATEGMED1/235773/19/NCBR/2016; AMC and MAC were sup-
ported by grant budget funds from NCBiR—Grant No. PBS3/A7/22/2015; MAC
was supported by budget funds from NCN—Grant No. 2012/05/B/NZ1/00024; IG
wassupportedbybudgetfundsfromNCN—GrantNo.NN303548139;KKKwas
supportedbybudgetfundsfromNCN—GrantNo.2013/11/N/NZ3/00186;andMZ
was supported by budget funds from NCN—Grant No. 2012/05/B/NZ4/02536.
xi
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Elzbieta Jastrzebska and Zbigniew Brzozka
2 Microfluidic Systems. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Sandra Skorupska, Elzbieta Jastrzebska, Michal Chudy, Artur Dybko
and Zbigniew Brzozka
3 Lab-on-a-chip Systems for Cellomics—Materials
and Technology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Dominika Kalinowska, Katarzyna Tokarska, Ilona Grabowska-Jadach,
Artur Dybko and Zbigniew Brzozka
4 Organ-on-a-chip Systems. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
Aleksandra Szuplewska, Michal Chudy and Zbigniew Brzozka
5 Biological Bases ofCardiac Function and the Pro-regenerative
PotentialofStem Cells in the Treatment ofMyocardial Disorder ... 79
Karolina Anna Bednarowicz and Maciej Kurpisz
6 Pluripotent and Mesenchymal Stem Cells—Challenging Sources
for Derivation of Myoblast . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
Karolina Archacka, Edyta Brzoska, Maria A. Ciemerych,
Areta M. Czerwinska, Iwona Grabowska, Kamil K. Kowalski
and Malgorzata Zimowska
7 Microfluidic Systems for Cardiac Cell
Culture—Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
Elzbieta Jastrzebska and Zbigniew Brzozka
8 Heart-on-a-chip Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
Magdalena Bulka and Elzbieta Jastrzebska
xiii
