4.1. Tissue distribution

Interestingly, MSCs reside in diverse tissues throughout the adult organism [25]. Nowadays, MSC populations have been obtained from many tissues other than the bone marrow, [26] including the adipose tissue [27] and placenta [28].

#### 4.2. Properties

Mesenchymal/stromal cells (MSCs) have the ability to differentiate into a variety of different cells/tissue lineages; osteoblasts, chondroblasts, adipoblasts and reticular stromal cells [29]. MSCs possess potent immunomodulatory and anti-inflammatory effects and have been used as agents in autoimmune diseases [30]. They interfere with pathways of the immune response by means of direct cell-to-cell interactions and soluble factor secretion. In vitro, MSCs inhibit proliferation of T cells, B-cells, natural killer cells and dendritic cells [31].

matrix metalloproteinases (MMP) - which are lytic enzymes required to cleave the components of the basement membrane - the gelatinases MMP-2 and MMP-9 are the most important because they specifically degrade collagen and gelatin components of the basement

Stromal Cell Ultrastructure

31

http://dx.doi.org/10.5772/intechopen.76870

MSCs isolated directly from bone marrow are positive for CD44. They are also positive for CD29, CD73, CD90, CD105 and CD166. On the other hand, they are negative for the hematopoietic surface markers such as CD11b, CD45, CD31, CD106, CD117 and CD135 [36]. As progress in phenotyping the MSCs and its progeny continues, the use of selective markers has resulted in the enhanced propagation and enrichment of the MSC population, while maintaining them in an undifferentiated state without diminishing the differentiation

A part of a work [38] was carried out at Department of Trauma, Hand and Reconstructive Surgery, Johann-Wolfgang-Goethe University Hospital, Frankfurt, Germany. They demonstrated that MSCs expressed typical MSCs specific antigens CD73, CD90 and CD105 (hematopoietic surface marker) and were negative for the hematopoietic marker and lymphocytic markers CD34, CD45, respectively. According to the International Society of Cell Therapy, CD73, CD90 alongside CD105 are positively expressed on MSCs and remain the primary molecules used to identify MSCs [39]. The phenotypic characterization of MSCs from bone marrow has been further realized through the identification of the cytokine expression profile of undifferentiated cells. Constitutive expression of cytokines, such as granulocyte-colony stimulating factor, stem cell factor, leukemia inhibitory factor, macrophage-colony stimulating factor, and IL-6 and IL-11 is consistent with the ability of MSCs to support hematopoiesis [40].

In order to avoid patient morbidity, the amount of MSCs that could be isolated from BM aspirate should be too small [12]. Therefore, they should be cultured in vitro to enable the expansion of MSCs to generate millions of cells which can be used for further therapeutic applications [39]. It was stated that MSCs retain more potential to differentiate after the third passage (P) [41]. In addition, over 70% of clinical trials used MSCs from 1 to 5 passages [42]. Moreover, a study reported that MSCs from 7 to 9 passages underwent osteogenic differentiation more than cells of later passages. Moreover, recent data indicated that reactive oxygen specieshandling mechanisms (i.e., antioxidative activity/reduction potential) become disrupted in later

Although several researchers [41] showed that with the long-term expansion of MSCs and with several sub-culturing, the cells lose their differentiating ability, a study performed [44] reported that no change at the level of genetic expression or differentiation capability of longterm cultured MSCs. Furthermore, MSCs have a stable phenotype over many generations

passages, a condition, which was not observed in the lower passage [43].

membrane [35].

potential [37].

5. Culturing

4.5. Characterization
