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      Designing compartmentalized hydrogel microparticles for cell encapsulation and scalable 3D cell culture

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          Abstract

          Compartmentalized hydrogel microparticles with high production rate, uniform size and shape, and tunable ECM support were developed for various scalable 3D cell culture applications.

          Abstract

          We describe here designs of compartmentalized hydrogel microparticles with a tunable extracellular matrix (ECM) support for cell encapsulation and scalable 3D cell culture. The microparticles, rapidly formed by a one-step, multi-fluidic electrostatic spraying technique (>10 000 min −1), have a uniform spherical shape, a nearly monodisperse size distribution and controlled compartmentalization. They not only have a high surface area for mass transfer but also offer defined space and essential ECM support for various scalable and efficient 3D cell culture, co-culture and microtissue production applications.

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          Most cited references45

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          Hypoxia signalling in cancer and approaches to enforce tumour regression.

          Tumour cells emerge as a result of genetic alteration of signal circuitries promoting cell growth and survival, whereas their expansion relies on nutrient supply. Oxygen limitation is central in controlling neovascularization, glucose metabolism, survival and tumour spread. This pleiotropic action is orchestrated by hypoxia-inducible factor (HIF), which is a master transcriptional factor in nutrient stress signalling. Understanding the role of HIF in intracellular pH (pH(i)) regulation, metabolism, cell invasion, autophagy and cell death is crucial for developing novel anticancer therapies. There are new approaches to enforce necrotic cell death and tumour regression by targeting tumour metabolism and pH(i)-control systems.
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            Microencapsulated islets as bioartificial endocrine pancreas.

            F. Lim, A Sun (1980)
            Single implantation of microencapsulated islets into rats with streptozotocin-induced diabetes corrected the diabetic state for 2 to 3 weeks. The microencapsulated islets remained morphologically and functionally intact throughout long-term culture studies lasting over 15 weeks.
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              Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche.

              The in vitro analysis of intestinal epithelium has been hampered by a lack of suitable culture systems. Here we describe robust long-term methodology for small and large intestinal culture, incorporating an air-liquid interface and underlying stromal elements. These cultures showed prolonged intestinal epithelial expansion as sphere-like organoids with proliferation and multilineage differentiation. The Wnt growth factor family positively regulates proliferation of the intestinal epithelium in vivo. Accordingly, culture growth was inhibited by the Wnt antagonist Dickkopf-1 (Dkk1) and markedly stimulated by a fusion protein between the Wnt agonist R-spondin-1 and immunoglobulin Fc (RSpo1-Fc). Furthermore, treatment with the gamma-secretase inhibitor dibenzazepine and neurogenin-3 overexpression induced goblet cell and enteroendocrine cell differentiation, respectively, consistent with endogenous Notch signaling and lineage plasticity. Epithelial cells derived from both leucine-rich repeat-containing G protein-coupled receptor-5-positive (Lgr5(+)) and B lymphoma moloney murine leukemia virus insertion region homolog-1-positive (Bmi1(+)) lineages, representing putative intestinal stem cell (ISC) populations, were present in vitro and were expanded by treatment with RSpo1-Fc; this increased number of Lgr5(+) cells upon RSpo1-Fc treatment was subsequently confirmed in vivo. Our results indicate successful long-term intestinal culture within a microenvironment accurately recapitulating the Wnt- and Notch-dependent ISC niche.
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                Author and article information

                Journal
                JMCBDV
                Journal of Materials Chemistry B
                J. Mater. Chem. B
                Royal Society of Chemistry (RSC)
                2050-750X
                2050-7518
                2015
                2015
                : 3
                : 3
                : 353-360
                Affiliations
                [1 ]Department of Biological and Environmental Engineering
                [2 ]Cornell University
                [3 ]Ithaca
                [4 ]USA
                [5 ]Weill Medical College of Cornell University
                [6 ]New York
                Article
                10.1039/C4TB01735H
                32262039
                3fbd36a7-94c4-4f16-ab16-f99b12592643
                © 2015
                History

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