7.1. Natural killer (NK) cells

formation and loss, show two strong models of transcriptional regulation of osteogenesis, and

MSC adipogenesis is stimulated by the nuclear hormone receptor peroxisome proliferatoractivated receptor γ (PPARγ) but at the same time it represses osteogenesis. Through binding to various ligands, like long-chain fatty acids and thiazolidinedione compounds, PPARγ induces the transactivation and transrepression of PPARγ. The bipotent coregulators TAZ function as a coactivator of Runx2 and as a corepressor of PPARγ, thus promoting osteogenesis while blocking adipogenesis [23]. In general, osteogenic genes are corepressed by a coactivator of adipogenic genes, but the opposite is also possible. This type of cellular effi-

Stretch-related mechanoinduction represents another interesting example of exchange between transcriptional cofactors of adipogenesis. If stretch is induced on mouse embryonic lung mesenchymal cells they form myocytes but they form adipocytes if uninduced. This occurs through activation of specific isoforms of tension-induced/inhibited proteins (TIPs) [24] chromatin-modifying proteins with intrinsic HAT activity that have other distinctive domains such as nuclear receptor-interacting motifs. TIP-1 which is expressed under nonstretch conditions provides a potential mechanistic endpoint for cytoplasmic RhoA-mediated of adipogenesis; induces RhoA signaling which stimulates adipogenesis [25]. Whereas TIP-3 induces myogenesis. These findings propose a molecular model that connects cell morphology mechanical induction cytoskeletal signaling and transcriptional response during MSC

The majority of studies of myogenesis in adult stem cells target skeletal muscle-derived stem cells, or satellite cells. The highly successful stimulation of myogenesis from adult stromal MSCs happened after transfection with activated Notch 1. Other studies, mainly target cardiomyogenesis, represented the importance of cell-cell contact in stimulating cardiomyogenesis through cocultured MSCs and cardiomyocytes, and the stimulation of MSC cardiomyogenesis in a rat

In normal conditions, the MSCs are present in low numbers, and on induction of myocardial infarction (MI) these cells proliferate rapidly to participate in wound healing, by generation of

After MI, MSCs penetrate the injured tissue by trafficking through the ECM and repairing the cardiac function. This is through production of HGF by apoptotic cardiomyocytes, and not by necrotic cardiomyocytes. MSCs are attracted to the apoptotic cell death site by HGF receptor MET, which are responsible for activation of a wide range of signaling pathways. Platelets migrate MSCs to the apoptotic cardiac cells by means of the interaction of a nuclear protein with TLR-4 expressed on MSCs; high mobility group box-1 (HMGB1). On activation of platelet, HMGB1/TLR-4 downregulate MET on MSCs, thus, decreasing the recruitment of the cells.

intramyocardial infarct model by Jagged 1, a Notch ligand [26].

ciency is very likely, allowing that MSCs may be differentiated to both lineages.

potentially other MSC lineage differentiation programs.

8 Stromal Cells - Structure, Function, and Therapeutic Implications

6.3. Adipogenesis

adipogenesis induction.

fibroblasts and myofibroblasts.

6.4. Myogenesis

MSCs are capable of inhibiting proliferation and function of NK cells, mediated by IDO, PGE2, and TGF-β1. Many studies have reported that MSCs only partially inhibit the proliferation of activated NK cells and are susceptible to lysis by activated cells. HLA-G5 inhibits NK cell mediated cytolysis and decreases interferon-gamma (IFN-γ) secretion [32].
