6.1. Chondrogenesis

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

3. MSCs must have the capacity to differentiate into osteoblasts, adipocytes, and chondroblasts

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

1. Differentiation of recruited MSCs into functional cells to replace damaged cells, permitting

2. Response of MSCs to inflammatory cytokines, prepares the microenvironment through production of immune regulatory factors that modulate the progression of inflammation

Furthermore, MSCs also produce a large amount of cytokines, chemokines, and GFs, which stimulate angiogenesis, prevent apoptosis, block oxidation reactions, promote remodeling of

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

MSCs are defined by a small cell body with a few long and thin cell processes. The nucleus is round and large with a prominent nucleolus, in the midst of finely spread chromatin particles, providing the nucleus a clear appearance. A small amount of rough endoplasmic reticulum, polyribosomes, Golgi apparatus and mitochondria are also present. The adjacent extracellular matrix is populated

The identification of specific signaling networks and 'master' regulatory genes that control unique MSCs differentiation lineages represents a major challenge. Obtaining a desired differentiation program, or preventing false differentiation of MSCs, needs ability to modulate biological effectors for effective clinical application, as in tissue engineering and regeneration.

The effects of MSCs are generally achieved through two mechanisms:

by affecting dendritic cells, B cells, T cells, and macrophages.

extra cellular matrix, and induce the differentiation of tissue stem cells [10].

by a few reticular fibrils however other types of collagen fibrils are absent [12].

CD19 and HLA-DR surface molecules;

6 Stromal Cells - Structure, Function, and Therapeutic Implications

the treatment of organ damage [9].

under in vitro conditions.

larger range of patients [9].

organ [11].

5. Morphology

6. Differentiation capacity

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 transactivation capability [17].

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 target genes.
