3D cellular culture

Several trials have been already done to produce a three dimensional support to grow cells. Collagen matrix, gelatin, nanofibers are some examples and each of them has some problems or limitations that have not allowed to be selected as a method of choice for three dimensional cell culture up to date. The advantage of three dimensional cell culture is to restore the normal environment where one cell is located into the tissue or in organism. The monolayer on a plastic surface or a suspension avoids the interaction with matrix or with other cells and, as a consequence, it affects cellular behavior. Furthermore, the plastic surface cannot be deformed in a similar way like the matrix and cells partially loss their plasticity. Matrigel and gelatin or collagen layer may help to maintain the three dimensional conformation of cells, but at the same time they are not totally inert surface and may activate some signaling pathways usually silenced. A possible alternative to matrigel or collagen layer is paper. Yes, the normal chromatographic paper has been proposed as a possible support to grow three dimensional cell culture. A recent paper published in PNAS journal describes this protocol. Scientists soaked the chromatography paper in hydrogel and cells and papers were layered at the bottom of tissue dish. In this way, cells were able to grow in contact with other cells cultured in the upper paper. To analyze one layer it was possible to peel the paper from the stack and work on it. The major advantage of the method, rather the low cost, is to sample a living tissue without fixing it or making thin sections. You can split the tissue and put inside the paper layer and when you want to analyze it, you just have to open it. In contrast, the main limitations are the lack of vascularization that is normally present in the natural tissue and the impairment of fluid flow. Thus, further work has to be done to make possible the local fluid flow that is really important in certain studies to study, for instance, the pharmacodynamic of drugs. Of course, even if this model is really interesting, as well as other three dimensional supports, it cannot substitute the use of animal model in science for many reasons. In particular, animals have vasculature, time dependent physiological and pathological remodeling, inflammation and immune system that are not present in any three dimensional in vitro model. All these elements are fundamental to understand the biological mechanism of pathways and characterize new drugs. In conclusion, paper support seems a very interesting model to study preclinical development of drug or to deep cell cell interactions and further applications will be published soon.