Different approaches in regenerative medicine: modulation of biological properties of human mesenchymal stem cells and induction of cardiomyocyte proliferation

The term “regeneration” defines a process which aims at the re-establishment of the morphological and physiological functions of damaged tissues and organs. The human body uses its own tissue-resident stem cells to repair adult tissues and organs, and to counteract senescence-related processes. Human mesenchymal stem cells show many useful and promising properties, such as self-renewal, multilinear differentiation, and isolation from almost all organs, in the regenerative medicine and cell therapy fields. Unfortunately, the human heart regeneration after injury is almost absent, and scars occurs. Several approaches have been used to improve the regenerative process, such as the use of satellite cells, cardiac stem cells, or other adult stem cells, but the results have been poor. In heart regeneration, the most promising strategy appears to promote the dedifferentiation and re-entry into cell cycle of cardiomyocytes. The aim of the study was to find new cellular strategies that could be useful in regenerative medicine. On the one hand, several “well-being” molecules (Leu-enkephalin, Met-enkephalin, β-endorphin, Oxytocin and Cannabidiol) have been tested to evaluate their effects on stem cells isolated from human adipose tissue, trying to reduce their senescence process, and promoting their differential ability. The results obtained indicate that Oxytocin and Cannabidiol were able to modulate the differentiative ability of stem cells (osteogenic and adipogenic, respectively), thus being interesting for the application of stem cells in regenerative medicine. On the other hand, we tested pro-inflammatory cytokines and growth factors alone or in association to assess the best combination that allowed the de-differentiation and re-enter in cell cycle of neonatal mice cardiomyocytes. Preliminary results showed that the administration of pro-inflammatory cytokines prior the administration of growth factors resulted the best condition to promote cardiomyocyte proliferation. Further investigations need to be assessed to deeply understand the molecular pathways behind our results.