Extracellular matrix microenvironment

Multiple applications for resilin-like polypeptides have garnered renewed research interest since the report of the first recombinant resilin in 2005. The excellent mechanical properties of the resilin-like polypeptides has directed investigation toward their use as high-performance materials and in tissue engineering applications. It is widely acknowledged that cells interact and take cues from their microenvironment and, therefore, the development of polymeric scaffolds to mimic the extracellular matrix and drive desired cell or tissue responses has been of wide interest. To this end, our laboratories have developed a modular resilin-like polypeptide (RLP12) (see Fig. 20) that contains not only twelve repeats of the... 

As outhned earUer every single step of hematopoiesis is regulated and controlled in vivo by the cell s microenvironment. This not only includes the composition and concentration of growth factors, but also the local oxygen concentration, the pH, the osmolaHty, the supply of nutrients and the cellular and molecular surrounding of the cells (cell-cell contact, adhesion molecules and extracellular matrix). All these parameters affect the fate of the cell and, to estabUsh a cell culture process to cultivate or generate a specific subpopulation, the influence of all these factors has to be considered in the experimental set-up. In the following sections these parameters will be discussed in brief. 

In conclusion, it is generally believed that the extracellular matrix of the cumulus oophorus functions as a selective filter permitting only those sperm that have not completed the acrosome reaction to penetrate to the zona pellucida. This matrix may also provide a unique microenvironment that regulates the final stages of capacitation. 

It has been shown that stem cell self-renewal and differentiation rates are influenced by their microenvironment, termed stem cell niche [107, 108]. The stem cell niche consists of the following components (1) extracellular matrix [109] (2) biochemical factors including cell-cell and cell-mahix interactions, localized soluble stimuli and gradients of soluble factors like growth factors and glucose concentration [ 110,111] ... 

Although most patients will respond to Imatinib it is not curative as minimal residual disease can be detected at the molecular level in the bone marrow. Mutations within the kinase domain of Bcr-Abl which can inhibit drug binding is known to contribute to clinical resistance. Additional mechanisms of resistance include the activation of Bcr-Abl independent survival pathways and overexpression of drug transporters. Finally an active area of research is to determine the contribution of the microenvironment of the bone marrow were minimal residual disease is typically found. Determining whether specific soluble factors or extracellular matrixes produced by the bone marrow microenvironment contributes to imanitib resistance may lead to combination therapies targeting minimal residual disease within the bone marrow compartment. 

Normal SCs are found to harbor in a specialized microenvironment called the stem cell niche , which contains capillaries, vascular endothelial cells, pericytes, and the fibrous proteins of the extracellular matrix. Other stromal cells, immune cells, and nerves may also be present in the niche [45]. Stimuli from the niche as well as signals from SCs themselves and from outside of niche, together, establish a regulatory network to balance between SC self-renewal and differentiation [46]. Under physiological conditions, the niche provides a tight control over proliferation, typically maintaining cells in GO and/or balancing... 

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