The Adequacy of Experimental Models and Understanding the Role of Non-coding RNA in Joint Homeostasis and Disease

RNA-mediated processes by non-coding RNA (ncRNAs) namely microRNAs, long ncRNAs and circular RNAs, as all epigenetic mechanisms are particularly sensitive to the effects of tissue microenvironment and environmental factors. In recent years research has focused on the development of smart cell culture in vitro systems one step closer to natural conditions, paying particular attention to the cellular microenvironment and cell culture conditions. 3D cell culture and co-culture systems based on cultivating a single cell population or different cell populations combined together, have found growing interest as useful tools to better understand cell biology and to offer more physiological relevant results by tightly controlling experimental parameters. The development of these in vitro models is a promising approach even if the limited availability of human tissue from which to obtain the cells have to take into account. Such an approach by using tissue specimens of human origin can allow the realization of suitable 3D in vitro models overcoming the limits of traditional 2D monolayer cell cultures, or expensive animal models that often cannot accurately recapitulate human etiopathogenesis and are not suited to develop novel drugs. It is widely recognized that in a 3D environment cells tend to be more subjected to morphological and functional changes differently to those grown in simplistic cellular monolayer. Another important issue is the methods matter regarding the employment of cell culture conditions that have to take into account the physiological parameters such as oxygen concentration, chemical and biophysical components. The applicability of results from in vitro studies to in vivo situations, especially as regards the molecules involved in regulatory mechanisms, is directly dependent on the degree of similarity between the in vitro experimental condition and the in vivo environment. We believe a major effort and investment of time in this direction by the scientific community is necessary. The effort should be toward the improvement and the use of technology which allows cells from a specific donor to grow and behave in vitro in a manner that more closely represents that experienced by their native counterparts. This approach will likely have a significant impact on the understanding the real role of critical regulators of tissue homeostasis such as ncRNAs, and on improving drug discovery. This objective can be achieved through different types of initiatives that connect the scientists who deal with joint homeostasis and disease, such as: (1) the creation of an international research Consortium dedicated to support the development and optimization of 3D cell culture models, (2) specific workshops for promoting the development of guidelines in order to minimize controversies on mechanisms of disease and potential therapeutic targets, (3) the creation of a blog managed by a joint scientific organization that promotes debate and where it is possible to meet the experts. Certainly the biggest challenge is to convince those scientists to move from their already well-established 2D, and often successfully funded, cellular models. Therefore, we think that a critical point is represented by adequate funding policy that takes these issues into account and makes ad hoc funds available for studying and developing more relevant experimental models.