<div>The advantages and applications of 3D cell cultures</div>


<div>Maddaly Ravi</div>


<div>Professor, Department of Human Genetics, Sri Ramachandra Medical College
and Research Institute, Porur, Chennai, India.</div>


<div>This back-story is about the paper published in Journal of Cellular
Physiology titled “3D cell culture systems: Advantages and
applications” whose citation is as follows:</div>


<div>Maddaly Ravi, V. Paramesh, S.R. Kaviya, E. Anuradha, and F.D. Paul
Solomon. 3D Cell Culture Systems: Advantages and Applications J. Cell.
Physiol. 230: 16–26, 2014.</div>


<div>Cell cultures are important material of study for the variety of
advantages that they offer. Both established continuous cell lines and
primary cell cultures continue to be invaluable for basic research and
for direct applications. Technological advancements are necessary to
address emerging complex challenges and the way cells are cultured in
vitro is an area of intense activity. An important advancement in cell
culture techniques has been the introduction of three dimensional
culture systems. This area is one of the fastest growing experimental
approaches in life sciences. Augmented with advancements in cell imaging
and analytical systems, as well as the applications of new scaffolds and
matrices, cells have been increasingly grown as three dimensional
models. Such cultures have proven to be closer to in vivo natural
systems, thus proving to be useful material for many applications.</div>


<div>Cell lines, especially cancer cell lines, have contributed immensely in
understanding the complex physiology of cancers. They are excellent
material for studies as they offer homogenous samples without individual
variations and can be utilised with ease and flexibility. Also, the
number of assays and end-points one can study is almost limitless; with
the advantage of improvising, modifying or altering several variables
and methods. Literally, a new dimension to cancer research has been
achieved by the advent of 3-Dimensional (3D) cell culture techniques.
This approach increased many folds the ways in which cancer cell lines
can be utilised for understanding complex cancer biology. 3D cell
culture techniques are now the preferred way of using cancer cell lines
to bridge the gap between the ‘absolute in vitro’ and ‘true in vivo’ and
we continue our work using such in vitro models. The aspects of cancer
biology that 3D cell culture systems have contributed include
morphology, microenvironment, gene and protein expression,
invasion/migration/metastasis, angiogenesis, tumour metabolism and drug
discovery, testing chemotherapeutic agents, adaptive responses and
cancer stem cells.</div>


<div>Our MSc in Human Genetics program includes a dissertation project
component which the students pursue in their final semester of their
4-semester course. As a faculty member, I had 2 students assigned to me
(the authors of the paper in discussion, Ms. S.R. Kaviya and Mr. V.
Paramesh) and my role was to be their dissertation project mentor and
guide. As was my field of interest, I chose to work with 3D cultures
with the two students assigned. This time again, as how I always
approached (and continue to approach) student projects, one of the first
steps would be to make them understand the requirement for a thorough
review of literature before working on a project. Apart from making them
understand the significance of thorough review of the available
literature, I also emphasize on the importance of scientific manuscript
writing and the manner in which manuscripts can be well prepared. Also,
one of our research scholars Ms. E. Anuradha was working on designing
scaffolds for tissue engineering applications at that time and was taken
on board for the review along with our Head of the Department Prof.
Solomon F.D. Paul.</div>


<div>Thus, the back story of the publication “3D cell culture systems:
Advantages and applications” began and we set out to initially arrive
at the components of the review; the aspects we wanted to cover in the
review. Once we had the review outline frozen, we started off on
collecting the literature available from all possible sources (the
primary, secondary and the tertiary) and analyzing/collating the
details. The details were filled into the components framework that we
decided for the review manuscript and we could complete the “sections”
of the manuscript.</div>


<div>After several revisions and editing, the net result was the
comprehensive review on the advantages and applications of 3D cultures
for studies involving differentiation, drug discovery for
pharmacological applications, as tumor models for cancer research, for
gene &amp; protein expressions, for cell proliferation &amp; cell-cycle
analysis, for studies involving cytoskeleton, apoptosis, cell adhesion,
cell signalling, cell motility, microenvironment, cell morphology,
tissue architecture, drug response, and cell behaviour as co-cultures as
the major components. Also, the various matrices and scaffolds used for
3D cultures were presented as a Table which gives the classification,
properties, salient features, and the specific appropriate applications
of the matrices and scaffolds.</div>


<div>We were happy that the manuscript took a good shape and turned out as
one which deals comprehensively in this exciting area of science. All
authors contributed equally for all aspects of manuscript preparation
and submission. Ms. Kaviya’s contribution for the formatting, and the
post-acceptance processes such as Galley proof corrections were
exemplary as with Ms. Anuradha’s contribution to the Table on scaffolds
and matrices. We thank the editors, the reviewers and the
editorial/production team of Journal of Cellular Physiology for the
entire process that happed from the manuscript submission till its
acceptance and finally, the publication of the manuscript. We are also
happy that the review continues to be among the top “most accessed”
papers of the journal from the time it was published on-line. The review
has obtained 106 citations till date (6th December
2017) in a little more than 2 years of its publication.</div>


<div>Now, the two PG students are well placed as research scholars and the
research scholar Ms. E. Anuradha had obtained her Doctorate and is
currently pursuing her post-doctoral career. Looking back at the story
beginning, it sure gives a good feel that 2 MSc students could author a
publication which was (and is) well received and they gained a firm
footing/understanding of the steps involved in research methodology.
Well, the three of us could author one more paper, this time, an
original research paper titled “Culture phases, cytotoxicity and
protein expressions of agarose hydrogel induced Sp2/0, A549, MCF-7 cell
line 3D cultures” published in the Journal ‘Cytotechnology’
(Cytotechnology (2016) 68:429–441; DOI 10.1007/s10616-014-9795-z). The
thorough review of literature sure helped us in what went into obtaining
a second publication with the 2 students as co-authors.</div>


<div>The story is still on and I do continue to work with 3D cultures of
cancer cell lines and I hope to contribute my miniscule bit to this area
of science, in whatever way I possibly can.</div>