Mimicking stem cell niches to increase stem cell expansion

Dellatore, Shara M.; Garcia, Ana Sofia; Miller, William M.

doi:10.1016/j.copbio.2008.07.010

Cited by 197 publications

(123 citation statements)

References 52 publications

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“…1A). 1 H NMR spectrum of methacrylated (MA)-alginate exhibited peaks of vinyl methylene and methyl protons at δ5.8 and 5.3, and 1.7, respectively, that were newly formed by the reaction of polymer with 2-aminoethyl methacrylate (AEMA) (Fig. S1).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Injectable preformed scaffolds with shape-memory properties

Bencherif

Sands

Bhatta

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

423

407

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Injectable biomaterials are increasingly being explored to minimize risks and complications associated with surgical implantation. We describe a strategy for delivery via conventional needle-syringe injection of large preformed macroporous scaffolds with well-defined properties. Injectable 3D scaffolds, in the form of elastic sponge-like matrices, were prepared by environmentally friendly cryotropic gelation of a naturally sourced polymer. Cryogels with shape-memory properties may be molded to a variety of shapes and sizes, and may be optionally loaded with therapeutic agents or cells. These scaffolds have the capability to withstand reversible deformations at over 90% strain level, and a rapid volumetric recovery allows the structurally defined scaffolds to be injected through a small-bore needle with nearly complete geometric restoration once delivered. These gels demonstrated long-term release of biomolecules in vivo. Furthermore, cryogels impregnated with bioluminescent reporter cells provided enhanced survival, higher local retention, and extended engraftment of transplanted cells at the injection site compared with a standard injection technique. These injectable scaffolds show great promise for various biomedical applications, including cell therapies.syringe-injectable hydrogels | cryogelation | shape retention | controlled delivery | cell therapy H ydrogels are 3D networks that can absorb a large amount of water while maintaining their structural integrity. They are considered as appropriate scaffolds for tissue engineering applications mainly due to their structural similarities with native soft tissue, and are widely used as soft materials in many biomedical applications including cell culture, cell encapsulation, controlled delivery of therapeutic agents, and medical device fabrication (1-6).Hydrogels typically exhibit a nanoporous network structure, but it is advantageous to use hydrophilic networks with large interconnected pores (>10 μm) to allow cell infiltration and deployment, and provide an increased surface area for cell attachment and interaction. As a result, macroporous hydrogel scaffolds have been developed using various techniques such as fiber bonding, gas foaming, microemulsion formation, phase separation, freeze-drying, and porogen leaching (7-15). More recently, gelation at subzero temperatures, known as cryogelation, has been used to create hydrogels with large interconnected pores (16-18). During cryogelation, the reactants are restricted to the unfrozen/semifrozen phases and form a cross-linked network upon polymerization, while the ice crystals nucleated from the aqueous phase during freezing function as porogens. The melting of these ice crystals at temperature above the freezing temperature gives rise to interconnected macroporous networks. Cryogels typically exhibit enhanced mechanical stability with respect to traditional hydrogels (17). Recent studies have shown the potential application of cryogels as tissue engineering scaffolds (19)(20)(21).Due to the trauma resulting fro...

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Section: Resultsmentioning

confidence: 99%

“…They are considered as appropriate scaffolds for tissue engineering applications mainly due to their structural similarities with native soft tissue, and are widely used as soft materials in many biomedical applications including cell culture, cell encapsulation, controlled delivery of therapeutic agents, and medical device fabrication (1)(2)(3)(4)(5)(6).…”

mentioning

confidence: 99%

Injectable preformed scaffolds with shape-memory properties

Bencherif

Sands

Bhatta

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

423

407

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“…The literature has a number of examples where ECM-based components were used to culture hES cells [24][25][26]. ECM proteins such as laminin [15], fibronectin [16] and vitronectin [17,18] adsorbed onto surfaces have been used for long-term propagation of hES cells.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the interface between adsorbed fibronectin and human embryonic stem cells

Kalaskar

Downes

Murray

et al. 2013

J. R. Soc. Interface.

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The cell-substrate interface plays a key role in the regulation of cell behaviour. Defining the properties of this interface is particularly important for human embryonic stem (hES) cell culture, because changes in this environment can regulate hES cell differentiation. It has been established that fibronectincoated surfaces can promote the attachment, growth and maintenance of the undifferentiated phenotype of hES cells. We investigated the influence of the surface density of adsorbed fibronectin on hES cell behaviour in defined serum-free culture conditions and demonstrated that only 25 per cent surface saturation was required to maintain attachment, growth and maintenance of the undifferentiated phenotype. The influence of surface-adsorbed fibronectin fragments was compared with whole fibronectin, and it was demonstrated that the 120 kDa fragment central binding domain alone was able to sustain hES cells in an undifferentiated phenotype in a similar fashion to fibronectin. Furthermore, hES cell attachment to both fibronectin and the 120 kDa fragment was mediated by integrin a5b1. However, although a substrateattached synthetic arginine-glycine-aspartic acid (RGD) peptide alone was able to promote the attachment and spreading of fibroblasts, it was inactive for hES cells, indicating that stem cells have different requirements in order to attach and spread on the central fibronectin RGD-cell-binding domain. This study provides further information on the characteristics of the cellsubstrate interface required to control hES cell behaviour in clearly defined serum-free conditions, which are needed for the development of therapeutic applications of hES cells.

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“…17,18,21,22 Modulation of Notch signaling Notch signaling was activated upon immobilization of soluble Jagged1 (Jag1; 10 mg/mL) or Delta1 (Dll1; 10 mg/mL) with Matrigel and was blocked by g-secretase inhibitor (GSI; DAPT 10 mM, Cat# D5942; Sigma-Aldrich) or hairy and enhancer of split 1 (HES1) small interfering RNA (siRNA) (100 nM; Dharmacon; sequences: ACGAGAGCAAGAAUAAAU, AGGCU GGAGAGGCGGCUAA, UCAACACGACACCGGAUAA, and ACUGCA UGACCCAGAUCAA) in developing embryoid bodies (EBs) and isolated hemogenic precursors. 14,17,23 Additionally, Notch signaling was altered by retroviral HES1 overexpression as we previously published 24 or short hairpin RNA (shRNA) knockdown in EBs. Four 29-mer shRNAs to target HES1 were generated using HuSH pGFP-V-RS plasmid vector (TG312478, Origene).…”

Section: Maintenance and Hematopoietic Differentiation Of Hescs And Imentioning

confidence: 99%