The progress in the understanding of tissue-specific


             The Organoid system is an in vitroculture system and is said to be one of the most important and most excitingdevelopments established in the world of biomedical research.

Organoid isanother way of culturing cell but in a more futuristic fashion as the 3Dtechnique was applied. To mke it short, Organoidsare three-dimensional (3D) cell cultures. And by cell cultures, these are thecells that have been selected, simplified and cultured in an artificial mediawhere in these cells could still highlight important features of therepresented organ such as liver, lungs, intestine and even brain. Theseorganoids can be collected from an adult stem cell; it contain a self-renewingstem cell population which differentiates into multiple, organ-specific celltypes.

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And collected organoids will be subjected to several processes and willbe grown a=in a special media that perfectly or at least, almost perfectlymimic their natural environment and survival requirements.             In the last ten years, there hasbeen a dramatic surge in the number of publications where single or groups ofcells are grown in substrata that have elements of basement membrane leading tothe formation of tissue-like structures referred to as organoids. However, thisfield of research began many decades ago, when the pioneers of cell culturebegan to ask questions we still ask today: How does organogenesis occur? How dosignals integrate to make such vastly different tissues and organs given thatthe sequence of the genome in our trillions of cells is identical? Here, wesummarize how work over the past century generated the conceptual frameworkthat has allowed us to make progress in the understanding of tissue-specificmorphogenetic programs. The development of cell culture systems that provideaccurate and physiologically relevant models are proving to be key inestablishing appropriate platforms for the development of new therapeuticstrategies. (Simian et al.

, 2016.)            That functional differentiation isdependent on 3D architecture has become accepted recently. Many papers over thelast 50 years have shown that cells cultured in 2D are not representative ofthe in vivo situation. Structurally, 2D cultures do not provide the conditionsfor the organization and cellular relationships observed in vivo. Moreover,cell signaling networks are altered in 2D versus 3D, and this probably explainswhy 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), Before2005, the word organoid was an extension of 3D cultures.

Typically, it referredto small tissue fragments taken from organs, mostly epithelial tissues,separated from stroma by mechanical and enzymatic digestion and grown indifferent 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 collagengels to produce a branching structure resembling branching in the mammary glandof virgin mice, or Fata et al. (2007), in which rodent mammary fragments were grown inlaminin-rich gels giving rise to alveogenesis. However, in the last decade, themeaning of “organoid” has lost precision and has come to cover a series of cellculture techniques that are not necessarily a single technique.

Below areexamples of definitions of organoids taken from some recent papers inappropriate journals for the field. We come across the following definitions:(1) “Varioussubfields use these terms either interchangeably or distinctly; for example, inthe field of mammary gland biology, the term organoids refers to primaryexplants of epithelial ducts into 3D extracellular matrix (ECM) gels.Conversely, in studies of intestinal biology, organoids can refer to clonalderivatives of primary epithelial stem cells that are grown without mesenchymeor can refer to epithelial–mesenchymal co-cultures that are derived fromembryonic stem cells or induced pluripotent stem cells” (Shamir and Ewald, 2014). (2) “Thus, we wouldlike to define an organoid as containing several cell types that develop from stem cells or organprogenitors and self-organize through cell sorting andspatially restricted lineage commitment, similar to the process in vivo” (Lancasterand Knoblich, 2014). (3) “Anorganoid is now defined as a 3D structure grown from stem cells and consisting of organ-specificcell types that self-organizes throughcell sorting and spatially restricted lineage commitment…” (Clevers, 2016). (4) “Here we definean organoid as an in vitro 3D cellular cluster derived exclusively from primarytissue, embryonic stem cells, or induced pluripotent stem cells, capable ofself-renewal and self-organization, and exhibiting similar organ functionalityas the tissue of origin” (Fatehullah et al.

, 2016).             It should be acknowledged that the development of theculture conditions that were established by scientists working on organoids (asoriginally defined) has contributed to the significant advances reported in thestem cell field in the last 10 years. Independently of the methods used togenerate the organoids and keep them in culture, these advances representoutstanding model systems to study human development and disease. For manyorgans, such as the brain, mouse and human development are not the same (Lancaster et al.

, 2013).             Moreover, induced pluripotent stem cells derived fromskin fibroblasts as well as 3D cultures of normal and diseased human organsoffer models for human diseases that are not easy to study in animal models (Lancaster et al., 2013).            Interestingly, the word organoid initially had adifferent meaning from all of the above. In the 1950s and 1960s, papersreferring 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 andcytoplasmic organoids in the living cell” (Duryee and Doherty, 1954). The wordorganoid was used also for tumors (Gordienko, 1964) or abnormalcellular growths (Wolter, 1967). Many papersdescribed 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 inthe future. These technologies are currently being explored in a range oftissue types and could have significant impact in medicine if attention is paidto functional differentiation and integrity of form and function maintainance.

At such time, these will be ready to be implemented not only in drug discoverybut also in patient treatment. The future will improve multi-organoid systems,also referred to as “body on a chip,” developing systems of increasedbiological complexity, where multiple organoids derived from different tissuesare brought together and allowed to integrate (Maschmeyer et al., 2015)                        Recent technical advances in thestem cell field have enabled the in vitro generation of complex structuresresembling whole organs termed organoids. Most of these approaches employthree-dimensional (3D) culture systems that allow stem cell-derived or tissueprogenitor 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 andre-create the original organ architecture. Since organoids can be grown fromhuman stem cells and from patient-derived induced pluripotent stem cells, theycreate significant prospects for modelling development and diseases, fortoxicology and drug discovery studies, and in the field of regenerativemedicine. Here, we outline historical advances in the field and describe someof the major recent developments in 3D animal organoid formation. Finally, weunderline current limitations and highlight examples of how organoid technologycan be applied in biomedical research. (Xinaris et al.

, 2015.)                        Knowing that the field has alreadybeen established and the scientists as well as the students aiming to becomethe best values the idea of science and the dimensionality of the context, wecan already assume that there would be a lot of advancements and clarificationsrelated to the Organoid System as well as in other tissue culturing complexes.  

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