The regeneration through stem cell of adipose origin
The human mesenchymal stem cells (hMSCs) can be obtained, as well as from bone marrow, classical source of initial isolation, also from alternative sources such as the dental pulp, the fetal membranes of the placenta at term and adipose tissue (“Adipose Derived Stem Cells , hASCs “). These cells are capable of reproducing processes of vasculogenesis and cardiovascular differentiation in vitro, and can also be used in vivo, to promote the repair of damaged hearts in animals subjected to myocardial infarction (53), or to improve the revascularization and functionality of pancreatic islets in diabetic rats (8). These results represent a proof of principle of the fact that, irrespective of the tissue of origin, the orientation towards a destiny vasculo-genic and vascular repair in vitro and in vivo represent a common denominator characterizing the potential therapeutic tissue of hMSCs.
Regardless of their source, hMSCs of different origins share the characteristic of being able to express a set of factors “trophic” (“secretome”) That could be secreted in different “environmental conditions” in vitro culture and “context” tissue in vivo. These factors identify a peculiarity of “paracrine” type of hMSCs that become so capable of acting through their secretome at the site of transplantation, inducing responses angiogenic, antiapoptotic and antifibrotic (7,26,31,53).
Although the bone marrow has been used in the past as the main source of hMSCs, the collection of such tissue is invasive and painful, placing the need of the identification of alternative sources of hMSCs. Furthermore, the use of hMSCs of bone marrow origin is potentially subject to a high degree of viral infections and by a significant decline of the vitality and differentiative potential of the same hMSCs with increasing age of the donor. For these reasons, an ideal source of hMSCs should: (i) be available in large quantities; (ii) be recoverable with a minimally invasive procedure; (iii) providing a population of hMSCs capable of maintaining a good vitality and a differentiation potential high even with increasing age of the donor (52). In recent years it has become increasingly evident as the adipose tissue possesses a population of multipotent stem cells, defined as precisely hASCs (16,47,52). The hASCs is a promising tool for cell therapy, since they can be used in vivo in animal models of acute myocardial infarction (25,33,46,48,55). In this regard, hASCs placed in culture were able to repair the infarcted myocardial tissue, acting as sources of paracrine mediators of trophic angiogenic processes (33). The hASCs can also be directed towards the fate of endothelial (5,14,32,36,37,38,44) and smooth muscle (1,4,15,21,22,29,30). There is increasing evidence in vitro and in vivo demonstrating the multipotency of ASCs in human and other species. These findings relate to the ability of ASCs to take the orientation toward the destinies adipocyte (18,43,56,57), condrocitario, (13,54,56,57), hematopoietic (9), hepatocyte (45,49,50 ), neuronal-like (23,27,40-42,56), osteoblastic (17,19,20,56,57), pancreatic (51) and skeletal muscle (28,34,56,57), in addition to the already those guidelines in myocardial and vascular sense.
Despite the progress in the isolation of hASCs, a number of issues remain unresolved, such as null cell survival or at least negligible after freezing and thawing of lipoaspirates, the difficulty of ex vivo expansion, the low efficiency of the “delivery” tissue (less than 5% of the transplanted cells are retained in the tissue after transplantation), and uncertain fate , also differentiation in vivo (3).
These issues minimize the benefits that can be obtained from the same cell expansion. In addition, the opportunity of a transfer of stem cells in the clinical area with relevant manipulation, including the ex vivo expansion in culture is significantly delayed by the need to comply with the requirements of the “guidelines” in respect of “major cellular manipulations” in accordance with the so-called “current good manufacturing practices” (“current Good manufacturing Practice, cGMP”) (39). However, these restrictions do not apply in the case of “manipulation irrelevant” [Regulation (EC) No 1394/2007 of the European Parliament and of the Council]. As this suggests, as it would be highly desirable for rapid clinical development of regenerative medicine technologies, the development of processing based on a “manipulation irrelevant” so as to obtain suitable products containing hASCs, ready for autologous use without any expansion, but also susceptible to cryopreservation and possible expansion in vitro.