The of tissue-like structures referred to as organoids.


            The Organoid system is an in vitro
culture system and is said to be one of the most important and most exciting
developments established in the world of biomedical research. Organoid is
another way of culturing cell but in a more futuristic fashion as the 3D
technique was applied. To mke it short, Organoids
are three-dimensional (3D) cell cultures. And by cell cultures, these are the
cells that have been selected, simplified and cultured in an artificial media
where in these cells could still highlight important features of the
represented organ such as liver, lungs, intestine and even brain. These
organoids can be collected from an adult stem cell; it contain a self-renewing
stem cell population which differentiates into multiple, organ-specific cell
types. And collected organoids will be subjected to several processes and will
be grown a=in a special media that perfectly or at least, almost perfectly
mimic their natural environment and survival requirements.


            In the last ten years, there has
been a dramatic surge in the number of publications where single or groups of
cells are grown in substrata that have elements of basement membrane leading to
the formation of tissue-like structures referred to as organoids. However, this
field of research began many decades ago, when the pioneers of cell culture
began to ask questions we still ask today: How does organogenesis occur? How do
signals integrate to make such vastly different tissues and organs given that
the sequence of the genome in our trillions of cells is identical? Here, we
summarize how work over the past century generated the conceptual framework
that has allowed us to make progress in the understanding of tissue-specific
morphogenetic programs. The development of cell culture systems that provide
accurate and physiologically relevant models are proving to be key in
establishing appropriate platforms for the development of new therapeutic
strategies. (Simian et al., 2016.)

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            That functional differentiation is
dependent on 3D architecture has become accepted recently. Many papers over the
last 50 years have shown that cells cultured in 2D are not representative of
the in vivo situation. Structurally, 2D cultures do not provide the conditions
for the organization and cellular relationships observed in vivo. Moreover,
cell signaling networks are altered in 2D versus 3D, and this probably explains
why drug screening outcomes many times do not reproduce the in vivo setting (Wang et al., 1998; Weaver et al., 2002)

            According to Simian et al.,(2016), Before
2005, the word organoid was an extension of 3D cultures. Typically, it referred
to small tissue fragments taken from organs, mostly epithelial tissues,
separated from stroma by mechanical and enzymatic digestion and grown in
different types of 3D gels to produce an organ-like structure. (Simian et al.,
2016) As an example, see Simian et al. (2001), in which rodent mammary fragments were grown in collagen
gels to produce a branching structure resembling branching in the mammary gland
of virgin mice, or Fata et al. (2007), in which rodent mammary fragments were grown in
laminin-rich gels giving rise to alveogenesis. However, in the last decade, the
meaning of “organoid” has lost precision and has come to cover a series of cell
culture techniques that are not necessarily a single technique. Below are
examples of definitions of organoids taken from some recent papers in
appropriate journals for the field. We come across the following definitions:

(1) “Various
subfields use these terms either interchangeably or distinctly; for example, in
the field of mammary gland biology, the term organoids refers to primary
explants of epithelial ducts into 3D extracellular matrix (ECM) gels.
Conversely, in studies of intestinal biology, organoids can refer to clonal
derivatives of primary epithelial stem cells that are grown without mesenchyme
or can refer to epithelial–mesenchymal co-cultures that are derived from
embryonic stem cells or induced pluripotent stem cells” (Shamir and Ewald, 2014).


(2) “Thus, we would
like to define an organoid as containing several cell types that develop from stem cells or organ
progenitors and self-organize through cell sorting and
spatially restricted lineage commitment, similar to the process in vivo” (Lancaster
and Knoblich, 2014).


(3) “An
organoid is now defined as a 3D structure grown from stem cells and consisting of organ-specific
cell types that self-organizes through
cell sorting and spatially restricted lineage commitment…” (Clevers, 2016).


(4) “Here we define
an organoid as an in vitro 3D cellular cluster derived exclusively from primary
tissue, embryonic stem cells, or induced pluripotent stem cells, capable of
self-renewal and self-organization, and exhibiting similar organ functionality
as the tissue of origin” (Fatehullah et al., 2016).


            It should be acknowledged that the development of the
culture conditions that were established by scientists working on organoids (as
originally defined) has contributed to the significant advances reported in the
stem cell field in the last 10 years. Independently of the methods used to
generate the organoids and keep them in culture, these advances represent
outstanding model systems to study human development and disease. For many
organs, such as the brain, mouse and human development are not the same (Lancaster et al., 2013).

            Moreover, induced pluripotent stem cells derived from
skin fibroblasts as well as 3D cultures of normal and diseased human organs
offer models for human diseases that are not easy to study in animal models (Lancaster et al., 2013).

            Interestingly, the word organoid initially had a
different meaning from all of the above. In the 1950s and 1960s, papers
referring to organoids often centered on intracellular structures (organelles),
with titles such as “Quantitative cine analysis of cell organoid activity” (Pomerat et al., 1954) or “Nuclear and
cytoplasmic organoids in the living cell” (Duryee and Doherty, 1954). The word
organoid was used also for tumors (Gordienko, 1964) or abnormal
cellular growths (Wolter, 1967). Many papers
described cases of “Organoid Nevus,” a circumscribed malformation of the skin,
most commonly in the scalp (Pinkus, 1976). 

            The directions and applications of the Organoid system in
the future. These technologies are currently being explored in a range of
tissue types and could have significant impact in medicine if attention is paid
to functional differentiation and integrity of form and function maintainance.
At such time, these will be ready to be implemented not only in drug discovery
but also in patient treatment. The future will improve multi-organoid systems,
also referred to as “body on a chip,” developing systems of increased
biological complexity, where multiple organoids derived from different tissues
are brought together and allowed to integrate (Maschmeyer et al., 2015)


            Recent technical advances in the
stem cell field have enabled the in vitro generation of complex structures
resembling whole organs termed organoids. Most of these approaches employ
three-dimensional (3D) culture systems that allow stem cell-derived or tissue
progenitor cells to self-organize into 3D structures. These systems evolved,
methodologically and conceptually, from classical reaggregation experiments,
showing that dissociated cells from embryonic organs can reaggregate and
re-create the original organ architecture. Since organoids can be grown from
human stem cells and from patient-derived induced pluripotent stem cells, they
create significant prospects for modelling development and diseases, for
toxicology and drug discovery studies, and in the field of regenerative
medicine. Here, we outline historical advances in the field and describe some
of the major recent developments in 3D animal organoid formation. Finally, we
underline current limitations and highlight examples of how organoid technology
can be applied in biomedical research. (Xinaris et al., 2015.)


            Knowing that the field has already
been established and the scientists as well as the students aiming to become
the best values the idea of science and the dimensionality of the context, we
can already assume that there would be a lot of advancements and clarifications
related to the Organoid System as well as in other tissue culturing complexes.




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