4. Characteristics

In 2006, the International Society of Cellular Therapy defined characterization of MSCs by the following three criteria [8]:

1. MSCs must be adherent to plastic under standard tissue culture conditions;

2. Certain cell surface markers must be expressed such as CD73, CD90, and CD105, other markers must not be expressed such as CD45, CD34, CD14, or CD11b, CD79 alpha or CD19 and HLA-DR surface molecules;

6.1. Chondrogenesis

transactivation capability [17].

target genes.

6.2. Osteogenesis

therapy of bone diseases.

There is similarity between chondrogenic differentiation of MSCs in vitro and of cartilage development in vivo. In MSC-derived chondrocytes, the following has been positively characterized: expression markers associated with chondrogenesis; including transcription factors (sox-9, scleraxis) and extracellular matrix (ECM) genes (collagen types II and IX, aggrecan, biglycan, decorin, and cartilage oligomeric matrix protein) [13, 14]. Many helpful signaling molecules, involving many transforming growth factor-β (TGF-β), bone morphogenetic protein (BMP), growth and differentiation factor (GDF) and Wnt ligands, have been recognized through naturally occurring human mutations and molecular genetic studies. Chondrogenesis of MSCs from a variety of mesodermal tissue sources is rapidly stimulated by recombinant proteins and/or adenoviral infection of MSCs with TGF-β1 and TGF-β3, BMP-2, BMP-4, BMP-6, BMP-12, BMP-13, and GDF-5 [14, 15]. Through specific intracellular Smad proteins and major mitogen-activated protein kinase (MAPK) cascades, TGF-βs and BMPs signal provide levels of specificity that are widely studied in MSC differentiation contexts, upon receptor binding [16]. Downstream MAPK signaling and Smad effectors crosstalk has declared that MAPK substrates include chromatin histone acetyltransferases (HATs). Smads recruit HATs which enhance Smad

Stromal Stem Cells: Nature, Biology and Potential Therapeutic Applications

http://dx.doi.org/10.5772/intechopen.77346

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Wnts possess double modulatory function in chondrogenesis. In human MSCs, Wnt7a induces chondrogenesis through various TGF-β1–MAPK signaling pathways when it is transiently upregulated, but in case of sustained expression, Wnt7a turns into chondroinhibitory [18]. Wnt3a controls bmp2 expression [19], providing a feed forward regulatory loop during chondrogenesis. In ATDC5 cells, chondrogenesis is inhibited by Wnt1 through upregulation of the mesodermal basic helix–loop–helix (bHLH) transcription factor, Twist 1 [20], this effect may be through involving negative sequestration of chondrostimulatory factors or direct repression of

Two bone morphogenic proteins (BMPs), especially BMP-2 and BMP-6, stimulate osteogenesis in MSCs. BMP-2 acts by induction the p300-mediated acetylation of Runx2, a master osteogenic gene, which leads to enhanced Runx2 transactivating capability. Histone deacetylases 4 and 5 stimulate the degradation of Runx2 by deacetylation, through Smurf1, Smurf2 and E3 ubiquitin ligases [21]. The cytokine TNF-α, involved in inflammation-mediated bone degradation, downregulates Runx2protein levels by increasing degradation by Smurf1 and Smurf2. BMPs, Runx2, and histone deacetyltransferases that are responsible for the therapeutic approaches to MSC-based bone tissue engineering, stimulate existing TNF-α based immuno-

Wnts is another important modulator in osteogenesis. Knockout and dosage compensation in Wnt-pathway-related transgenic animals provide the strongest proof that high levels of endog-

The exciting finding of transcriptional mechanisms, suggesting that a global osteogenic gene, runx2, and a specific osteogenic homeobox gene, tbx5, are responsible for the balance of bone

enous Wnts promote osteogenesis, whereas low levels inhibit osteogenesis [22].

3. MSCs must have the capacity to differentiate into osteoblasts, adipocytes, and chondroblasts under in vitro conditions.

MSCs generally have low immunogenicity as they do not express MHC class II or costimulatory molecules. Thus, injection of autologous or allogeneic MSCs has been employed in clinical studies. Allogeneic MSC therapy has the potential to expand MSCs therapy to a larger range of patients [9].

The effects of MSCs are generally achieved through two mechanisms:


Furthermore, MSCs also produce a large amount of cytokines, chemokines, and GFs, which stimulate angiogenesis, prevent apoptosis, block oxidation reactions, promote remodeling of extra cellular matrix, and induce the differentiation of tissue stem cells [10].

In addition, under the effect of signals of cellular damage, known as homing signals, MSCs migrate toward areas of injury. This migration property of MSCs is important in regenerative medicine, where various injection routes are utilized depending on the damaged tissue or organ [11].
