Engineering a stem cell house into a home

Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Stem Cell Research & Therapy (Impact Factor: 4.63). 01/2011; 2(1):3. DOI: 10.1186/scrt44
Source: PubMed

ABSTRACT In the body, tissue homeostasis is established and maintained by resident tissue-specific adult stem cells (aSCs). Through preservation of bidirectional communications with the surrounding niche and integration of biophysical and biochemical cues, aSCs actively direct the regeneration of aged, injured and diseased tissues. Currently, the ability to guide the behavior and fate of aSCs in the body or in culture after prospective isolation is hindered by our poor comprehension of niche composition and the regulation it imposes. Two-and three-dimensional biomaterials approaches permit systematic analysis of putative niche elements as well as screening approaches to identify novel regulatory mechanisms governing stem cell fate. The marriage of stem cell biology with creative bioengineering technology has the potential to expand our basic understanding of stem cell regulation imposed by the niche and to develop novel regenerative medicine applications.

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Available from: Penney Gilbert, Jun 07, 2014
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    • "For example, mesenchymal stem cells (MSCs), grown on collagen-coated polyacrylamide gels engineered to mimic the elasticity of tissues, upregulate markers indicative of differentiation towards cells of those tissues (Engler et al., 2006). The elastic modulus of hydrogels has previously been experimentally manipulated by varying acrylamide and bis-acrylamide concentrations (Engler et al., 2004) or the percentage of polyethylene glycol (PEG) polymer in solution (Gilbert and Blau, 2011; Kloxin et al., 2010a, 2010b). Interactions of cells with materials such as alginate (Lee and Mooney, 2012), collagen (Grinnell, 2003), hyaluronic acid (Shu et al., 2002), polyacrylamide (Engler et al., 2006), and polydimethylsiloxane (PDMS) (Tan et al., 2003) have all been extensively characterized. "
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    ABSTRACT: Our objective was to characterize the elasticity of hydrogel formulations intended to mimic physical properties that cells and tissues experience in vivo. Using atomic force microscopy (AFM), we tested a variety of concentrations in a variety of biomaterials, including agarose, alginate, the collagens, fibrin, hyaluronic acid, kerateine, laminin, Matrigel, polyacrylamide, polyethylene glycol diacrylate (PEGDA) and silicone elastomer (polydimethylsiloxane). Manipulations of the concentration of biomaterials were detectable in AFM measurements of elasticity (Young's modulus, E), and E tended to increase with increased concentration. Depending on the biomaterials chosen, and their concentrations, generation of tunable biocompatible hydrogels in the physiologic range is possible.
    07/2013; 27. DOI:10.1016/j.jmbbm.2013.07.008
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    • "A vision of in situ guided tissue regeneration strategies has been developed, where smart materials delivering peptide or small molecules with and without regenerative cells can be applied with minimally invasive techniques to enhance endogenous regeneration respecting (stem) cell biology and developmental processes (Gilbert and Blau 2011; Lutolf et al. 2009; Uebersax et al. 2009). Exciting developments in material science are capable of perfectly matching these scenarios using intelligent and functional materials, which can also be designed for perfect timely release of factors involved in regeneration (Astachov et al. 2011; Chen et al. 2010; Di Maggio et al. 2011; Dvir et al. 2011; Gilbert and Blau 2011; Grafahrend et al. 2010; Klinkhammer et al. 2010; Lutolf et al. 2009; Meinel et al. 2009; Votteler et al. 2010). Cellular and organismal aging phenomena in an elderly and diseased target population for regenerative strategies may be serious obstacles for successful treatment regimens. "
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    ABSTRACT: In situ guided tissue regeneration, also addressed as in situ tissue engineering or endogenous regeneration, has a great potential for population-wide "minimal invasive" applications. During the last two decades, tissue engineering has been developed with remarkable in vitro and preclinical success but still the number of applications in clinical routine is extremely small. Moreover, the vision of population-wide applications of ex vivo tissue engineered constructs based on cells, growth and differentiation factors and scaffolds, must probably be deemed unrealistic for economic and regulation-related issues. Hence, the progress made in this respect will be mostly applicable to a fraction of post-traumatic or post-surgery situations such as big tissue defects due to tumor manifestation. Minimally invasive procedures would probably qualify for a broader application and ideally would only require off the shelf standardized products without cells. Such products should mimic the microenvironment of regenerating tissues and make use of the endogenous tissue regeneration capacities. Functionally, the chemotaxis of regenerative cells, their amplification as a transient amplifying pool and their concerted differentiation and remodeling should be addressed. This is especially important because the main target populations for such applications are the elderly and diseased. The quality of regenerative cells is impaired in such organisms and high levels of inhibitors also interfere with regeneration and healing. In metabolic bone diseases like osteoporosis, it is already known that antagonists for inhibitors such as activin and sclerostin enhance bone formation. Implementing such strategies into applications for in situ guided tissue regeneration should greatly enhance the efficacy of tailored procedures in the future.
    Cell and Tissue Research 10/2011; 347(3):725-35. DOI:10.1007/s00441-011-1237-z · 3.33 Impact Factor
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    Stem Cell Research & Therapy 05/2011; 2(3):22. DOI:10.1186/scrt63 · 4.63 Impact Factor
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