## 4 Discussions  
SSc is a life-threatening disease with general critical implications and a wide range of oral manifestations [30]. It was reported that in SSc, resident MSCs might be dysfunctional and participate in disease progression, but this information is inconsistent [31; 32]. Since the academic literature associated with this topic reveals limited information and knowledge on the oral MSCs from SSCs, the proposed framework underlines the novelty of our study. Figure 3: Grafical representation of functionality tests. (**A**). Colony-Forming Units (CFU) test; (**B**) migration potential test. MSCs = mesenchymal stromal cells, hMSCs = healthy MSCs, SScgMSCs = gingival MSCs, SScgtMSCs = granulation tissue MSCs, SSc = systemic sclerosis; \({}^{**}\)\(p\)\(\leq\) 0.05. The present study isolated MSCs from gingiva and periapical granulation tissue from an SSc patient, characterized the isolated cells, and compared their properties to data concerning gingival MSCs isolated from a healthy patient in two different growing conditions. Isolation of MSCs from gingival and granulation tissues from SSc is not surprising as the oral cavity has proven to be an important source of progenitors [33; 34; 35; 36; 37]. The fulfillment of standard minimal criteria for defining multipotent MSCs [25] appears to confirm that isolated cells present the essential features of MSCs, such as plastic adhesion properties without phenotypic change, special surface antigen make-up, and differentiation potential. Both SSc-derived MSCs show a relatively reduced expression of surface antigens CD73, CD90, and CD105 in comparison to hMSCs, which is in agreement with the results reported by others [34; 38]. The inflammatory conditions could inhibit the expression of CD105 [38]. CD105 is a glycoprotein involved in the modulation of TGF-beta (transforming growth factor-beta) receptor signaling, which regulates cell morphology, migration, and proliferation, thus impacting MSCs and tumor growth and metastasis [39]. CD90 influences cell-cell and cell-matrix interactions, cell adhesion and migration, cytoskeleton organization, and tissue regeneration [40]. Reduced expression of CD90 was not associated with modifications of the morphology, proliferation rate, or immunosuppressive potential of MSCs, but augmented the differentiation potential of MSCs toward osteogenic and adipogenic lineages [41]. More recent information reported no significant differences in marker profiles of MSCs from SSC compared with healthy cells [42]. The results of this experiment demonstrate the potential of isolated MSCs to generate osteoblasts, adipocytes, and chondroblasts. However, prior research has found an alteration in the differentiation potential of MSCs into osteoblasts and adipocytes [11]. This biological multilineage differentiation property is a unique identification feature of MSCs [25]. Furthermore, the spontaneous generation of embryoid bodies in certain conditions also indicated the differentiation capabilities of MSCs. As shown by [PERSON] [43] and [PERSON] et al. [33], these embryoid bodies form three-dimensional multicellular aggregates of differentiated and undifferentiated cells. Additionally, it has also been revealed that embryoid bodies could comprise precursor cells to mesenchymal as well as neural stem cell lineages [11; 44; 45; 46; 47]. Overall, the study's findings suggest a reduced functionality of MSCs derived from SSc as compared to MSCs from healthy tissues, although recent data showed normal CFU-F capability of MSCs isolated from SSc and healthy patients [42]. CFU-F formation capacity was demonstrated for putative MSCs isolated from SSc. Additionally, CFU-F frequency was significantly lower for SSctMSCs than in the case of hMSCs (\(p\) = 0.05) and SSctMSCs (\(p\) = 0.004) in normal plating conditions. CFU-F frequency of SSctMSCs also remained lower than that observed for SSctMSCs (\(p\) = 0.09) in the HA-containing medium.