Three Dimensional Tissue Constructs

Tissue cellular variation is orchestrated by various biological processes that root from early formation and development of germ layers until late adulthood. The cellular organization, homeostasis and maintenance of each tissue are crucial for the normal function of organs and their harmonized co-function. The molecular pathways that control this balance within an organ differ accordingly with embryonic or adult age. Furthermore paracrine and endocrine factors that can be affected by environmental conditions may directly alter the balanced function of an organ, leading to the organ’s partial or complete failure to function (e.g. neurodegenerative diseases). It has been speculated that once a tissue cell population fails to reorganize itself, for instance after a stressful event, mechanisms of cell regeneration are activated, which under unknown abnormal conditions may lead to the formation of cancer initiating stem cell niches that may develop into a carcinogenic tissue (e.g. Glioblastoma Multiforme).

These multiple mechanisms that regulate organ formation and maintenance have been extensively studied and projected in in vivo studies (i.e. animal models and clinical trials), reflecting the actual conditions under which an intact or diseased organ survives. Although in vivo studies have been shown to cover the larger scale of research studies, regarding the discovery of molecular and cellular mechanisms that govern the development of a pathological condition within an organ, there are still limitations that in vitro studies can address. The major limitation of in vivo approaches is mainly the fact that the number of experimental samples available, i.e. animal models and human tissue samples, is limited, restricting for instance the study of large scale drug tests. Furthermore, in vivo studies most of the times cannot provide extensive information regarding the progress and especially the initiation of a disease. One such research topic is the unraveling of the mechanisms that regulate the threshold between a normal proliferating cell and a cancer initiating cell. During in vivo studies it is difficult to track a disease from the very beginning of it, something that can be overcome only by studying the disease in vitro, since the time point of disease initiation can be recorded.

In vitro studies are well established in many research areas and especially in cancer research. Most of the studies though are relying on two dimensional monolayers which show a high advantage in preclinical study analysis. Today’s research though emerges the need for the development of three dimensional tissue culture system which can mimic an intact and diseased tissue and/or organ, for the study of cellular, molecular and mechanistic properties of cells and cell population within an organ. This technology is the basis of a promising research field which might overcome the limitations of two dimensional cell culture models. It has been indicated that three dimensional models used in cancer research are more predictive of clinical trials, emanating the requirement for new protocols, techniques and technological materials that can promote in vitro generation of intact and diseased organs.

Nikolaos Mandalos
EPOS-IASIS Research and Development Ltd

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