Adipose-derived stem cells (ASCs) represents a promising tool not only for soft tissue engineering, but also for the treatment of severe pathologies, such as chronic intestinal inflammation, cardiovascular diseases and lung injury. Human ASC therapeutic efficacy is likely due to self-renewal properties, multilineage differentiation potential and immunomodulatory activity. Notwithstanding the use of ASCs in different clinical trials, the molecular mechanisms at the basis of their administration have to be fully elucidated. In particular, there is an urgent need to identify novel strategies aimed to a lifelong persistence of ASC properties for potentiating their therapeutic applications.
Non-coding RNAs (ncRNAs) and epigenetic changes, such as DNA methylation and histone modifications, have been suggested to have a role in the regulation of adult stem cell proliferation, vitality, differentiation potential and immunomodulatory capacities, since these molecular drivers can be finely tuned and reprogrammed. Importantly, many epi-molecules and ncRNAs can be secreted into micro-vesicles, the so-called secretome, which has recently emerged as a key factor in ASC-mediated paracrine effects, but the specific role in the different cellular processes has not yet been clarified.
In order to promote clinical applications of autologous ASCs, we aim to perform in vitro studies to assess the use of different epi-drugs and ncRNA-based approaches to boost ASC therapeutic characteristics, mainly immunomodulation, and to concomitantly reduce senescence mechanisms, which represent an important limit in cell-based therapies. Big data interrogation by using bioinformatic tools will help to identify key molecules and/or regulative pathways responsible for ASC properties, and would promote the development of new targeted strategies able to increase ASC plasticity and stability, so enhancing their efficacy in regenerative medicine of human pathologies.
