Adipose stem cells on the basis of tumor transformation

Mesenchymal stem cells thanks to their differentiated multipotent ability are considered the most promising candidate for tissue engineering and regenerative medicine. The source of mesenchymal stem cells up to about 20 years was represented by the bone marrow, but due to their limited amount of cells together with a very invasive and painfull surgical treatment, poorly accepted by patients, has led the scientific community to investigate an alternative mesenchymal stem cells source with similar properties. In particular, the adipose tissue has attracted the greatest interest thanks to its relative abundance, the easy of availability and the large amounts of mesenchymal stem cells which are obtenible. So this adipose stem cells subpopulation, once verified the same differentiation potential of them derived from bone marrow, represent the ideal type of adult mesenchymal stem cells useful for numerous regenerative and tissue engineering applications. In particular the bone regeneration, obtained after the lipotransfer of a specific stem cells subpopulation isolated from adipose tissue, should be considered one of the most successful applications in the field of regenerative medicine and tissue engineering. (Chapter 1). A further widespread use of mesenchymal stem cells is to reconstructive medicine. In particular, most patients with breast cancer, whenever possible, based on the type and stage cancer disease (Chapter 2), first make use of a demolitive surgery, in order to completely remove the tumor mass presence, and then resort to a reconstructive plastic surgery procedure. In breast cancer patients it is often used the adipose tissue as autologous filler. Even though the surgical treatment does not represent a potential danger for the patient, many scientific works have highlighted how the use of these self transplantations constitute a great risk for a possible cancer relapse despite the absence of a minimal residual disease. The presence of a mature adipocytes population infact, is responsible of a specific microenvironment, composed by pro-inflammatory cytokines and paracrine signals, that induce a generalized inflammatory state and which stimulate a proliferative return of those few quiescent cancer cells that still remain in the implantation site. In particular we have seen that the action of adipokines and interleukins generated by adipose autologous filler works both on differentiated tumor cells, just in a active proliferation cell phase but also on the cancer stem cell population that instead reside in a quiescent cell cycle phase. (Chapter 3). Therefore it is essential develop a more accurate and specific lipofilling procedure, especially going to select an appropriate autologous filler, in which a particular adipose stem cell subpopulation, with great regenerating properties has to be chosen among the adipose populations already present in conventional fillers. (Chapters 4). So the goal of this study is to enable the development of new selective therapies useful to remove the cancer stem cells, real responsible for tumor relapse. One of the most promising cancer therapies among those currently in the testing phase could be the differentiative therapy, and specifically one that uses the negative regulatory properties of the miRNAs (Chapter 5).