## 4 Discussions
When plated in HA-containing conditions, both SSc-derived cell lines (SSCgMSCs and SSctMSCs) migrated significantly less (\(p\) = 0.033 and \(p\) = 0.005, respectively) than hMSCs. These results are in agreement with data provided by other researchers [11; 44], while some studies reported no phenotype or functionality alterations in SSc-derived MSCs, compared to MSCs from healthy subjects [14; 48]. According to our results, SSctMSCs appeared to be more dysfunctional than SSctMSCs, as they displayed impaired CFU formation in both normal and HA-containing conditions. This confirms previous data [34; 37; 49] suggesting that MSCs stem cell properties could be impacted by inflammation [50] rather than the SSc per se. Other studies reported that MSCs derived from inflamed tissues showed resistance to inflammatory stimuli, as no impairments had been highlighted [26; 36; 51]. On the other hand, the functional disparities observed in the case of SSctMSCs should be considered as a direct effect of the general disease. The present study recorded a more dysfunctional behavior of SSc-derived MSCs as compared to hMSCs. Thus, the data from the present experiment suggest rejection of the null hypothesis. However, more oral samples derived from SSc patients should be analyzed in order to better \"portray\" the behavior of oral MSCs. However, there are still some underlying uncertainties with regard to the disparities of MSCs harvested from other SSc-associated regions. One explanation may lie in the fact that resident MSCs might be involved in SSc pathogenesis through different pathways such as an increase in TGF\(\beta\)-R2 (transforming growth factor, beta receptor II) at the surface of SSc-MSCs in comparison with the same type of healthy cells and an increased sensibility to TGF\(\beta\), which up-regulates this pathway and increases the synthesis of collagen 1 [52], the modification of the angiogenic capacity of MSCs due to overexpression of pro-angiogenic factors (i.e., VEGF-A vascular endothelial growth factor A) [53] and higher telomerase activity, inducing early senescence [11]. On the other hand, some data sustained that adipose tissue MSCs from SSc do not display the alterations observed in bone-marrow-derived MSCs [14]. In SSc, infusions with autologous adipose tissue MSCs would provide local and time-limited immunosuppression in comparison with conventional immunosuppressive [54]. However, recent data reported the potential contribution of white adipose tissue and the adipocyte lineages to the pathologic phenomena in SSc [55,56] and the loss of subcutaneous adipose tissue in SSc [57]. The mentioned shortcomings make these approaches more questionable than the allogeneic techniques that are presently recommended as the gold standard to treat SSc lesions [58]. Further studies should elucidate whether the impairments of progenitors are due to the pathological milieu or to the intrinsic modification of SSc pathogenesis pathways, and new research should assess diverse sources of MSCs from SSc patients and identify the lineages displaying the most appropriate properties [58] as potential treatment instruments of this general disease [54]. This sustains the novelty of our study in trying to identify new sources of MSCs with possibly better properties. MSCs of different tissular origins have relatively uniform surface antigenic markers but display various genetic fingerprints responsible for the secretion of specific biological active molecules that have particular therapeutic consequences [59]. From this perspective emerges another limitation of our study related to the lack of investigation of the genetic profile of experimental cell lines and quantification of the ability to differentiate, especially in adipocyte lines--important players sustaining the attenuation of some SSc subcutaneous lesions [60]. Efforts will be completed to develop further evaluations on these issues.