Use of small molecules to adjust the proliferation and differentiation of stem cells
One of the main challenges of regenerative medicine is the ability to fully exploit the multipotentiality of stem cells to allow the restoration, preservation and / or enhancement of tissue function. Stem cells can be a source of different cell types, thereby compensating for the inability of the adult to repair the damage to tissues that have lost the ability to innovate (Wagers 2012). In this context, the impact of application of methods aimed at controlled differentiation of stem cells are therefore potentially enormous, as usable for the care and treatment of a wide spectrum of degenerative diseases. Despite the availability of molecules able to control their proliferation, their differentiation, their motility, etc.. is still very limited.
In large part, this is due to:
-the complexity of the molecular mechanisms that regulate these functions;
-to the limitations of experimental approaches used.
It is therefore crucial the development of project / technology platforms targeted to the identification of regulators of stem cells through the development of new methodologies such as HTS and robotics / automation of processes (Desbordes, Placantonakis et al., 2008; Rubin 2008) .
The possibility of directing in a rational manner the differentiation of stem cells by altering signaling by the addition of small molecules represent a substantial step forward for the goals of regenerative medicine. The achievement of this objective could help to obtain cell cultures differentiated in a homogeneous way at reduced costs.
Although the literature describe numerous methods of cellular reprogramming through alteration of the transcriptional control (Cowan, Atienza, Melton, & Eggan, 2005; Meivar-Levy & Ferber, 2010; Takahashi et al., 2007), the mechanisms and signals that regulate the differentiation of stem cells through the modulation of signaling are not included.
We aim to make a contribution in this direction by using the system of murine mesoangioblasts (Cossu & White, 2003). Using a screening platform based on automated fluorescence microscopy (Sacco et al., 2012) we aim to identify molecules that can reprogram the differentiation of progenitor cells toward the skeletal muscle (Sampaolesi et al., 2006) or the smooth muscle (Tagliafico et al., 2004). The molecules identified programming in screening will be used to disrupt the cellular system in order to develop a predictive model that is able to infer the behavior of the system even under conditions that have not been tested experimentally (Sacco et al., 2012). This s analysis of the behavior of the model should provide new hypotheses on the utilization of combinations of perturbations of cellular pathways in order to improve efficiency of differentiation.