Signals from the surface modulate differentiation of human pluripotent stem cells through glycosaminoglycans and integrins

Wrighton, Paul J.; Klim, Joseph R.; Hernandez, Brandon; Koonce, Chad H.; Kamp, Timothy J.; Kiessling, Laura L.

doi:10.1073/pnas.1409525111

Cited by 58 publications

(62 citation statements)

References 49 publications

(66 reference statements)

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“…Generation of Cerebral and retina organoids (Nakano et al, 2012) relies on Matrigel, a murine source of ECM proteins, to induce self-organization, as do protocols for intestinal organoid generation (Sato et al, 2009). However, Matrigel can also provide signals inhibitory to differentiation (Wrighton et al, 2014), and the specific properties of this matrix responsible for organoid induction are unclear. Chemically defined matrix components would help elucidate the interplay between cell adhesive cues and mechanical forces in guiding condensate and organoid generation.…”

mentioning

confidence: 99%

Forces of Change: Mechanics Underlying Formation of Functional 3D Organ Buds

Wrighton

Kiessling

2015

Cell Stem Cell

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mentioning

confidence: 99%

Forces of Change: Mechanics Underlying Formation of Functional 3D Organ Buds

Wrighton

Kiessling

2015

Cell Stem Cell

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“…They then applied this array system to screen for peptides that can maintain long-term self-renewal of hPSC lines [37]. Recently, they applied the heparin-binding peptides discovered by the SAM peptide microarray to hPSC differentiation and elucidated the signal pathways switch between Akt and Smad for different germ layer cell differentiation [55]. …”

Section: Screening the Effects Of Materials Chemical Structures Onmentioning

confidence: 99%

“…To this end, Kiessling and coworkers have identified heparin-binding peptides by using microarray technology and elucidated how the binding interactions between substrates and cell surface receptors can switch signal pathways between Akt and Smad for different germ layer cell differentiation [55]. …”

Section: Perspective and Conclusionmentioning

confidence: 99%

Polymer microarray technology for stem cell engineering

2016

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Stem cells hold remarkable promise for applications in tissue engineering and disease modeling. During the past decade, significant progress has been made in developing soluble factors (e.g., small molecules and growth factors) to direct stem cells into a desired phenotype. However, the current lack of suitable synthetic materials to regulate stem cell activity has limited the realization of the enormous potential of stem cells. This can be attributed to a large number of materials properties (e.g., chemical structures and physical properties of materials) that can affect stem cell fate. This makes it challenging to design biomaterials to direct stem cell behavior. To address this, polymer microarray technology has been developed to rapidly identify materials for a variety of stem cell applications. In this article, we summarize recent developments in polymer array technology and their applications in stem cell engineering. Statement of significance Stem cells hold remarkable promise for applications in tissue engineering and disease modeling. In the last decade, significant progress has been made in developing chemically defined media to direct stem cells into a desired phenotype. However, the current lack of the suitable synthetic materials to regulate stem cell activities has been limiting the realization of the potential of stem cells. This can be attributed to the number of variables in material properties (e.g., chemical structures and physical properties) that can affect stem cells. Polymer microarray technology has shown to be a powerful tool to rapidly identify materials for a variety of stem cell applications. Here we summarize recent developments in polymer array technology and their applications in stem cell engineering.

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“…In particular, self-assembled monolayer (SAM) technology has received significant attention as it allows for versatile peptide functionalization strategies [19]. To this end, Kiessling and coworkers prepared thiolated peptides and spotted them onto gold-coated glass slides to prepare peptide-functionalized SAM microarrays [17, 20, 21]. Alternatively, Kilian and coworkers have taken advantage of recent advances in “click” chemistry [22].…”

Section: Introductionmentioning

confidence: 99%

Development of peptide-functionalized synthetic hydrogel microarrays for stem cell and tissue engineering applications

et al. 2016

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Synthetic polymer microarray technology holds remarkable promise to rapidly identify suitable biomaterials for stem cell and tissue engineering applications. However, most of previous microarrayed synthetic polymers do not possess biological ligands (e.g., peptides) to directly engage cell surface receptors. Here, we report the development of peptide-functionalized hydrogel microarrays based on light-assisted copolymerization of poly(ethylene glycol) diacrylates (PEGDA) and methacrylated-peptides. Using solid-phase peptide/organic synthesis, we developed an efficient route to synthesize methacrylated-peptides. In parallel, we identified PEG hydrogels that effectively inhibit non-specific cell adhesion by using PEGDA-700 (M. W. = 700) as a monomer. The combined use of these chemistries enables the development of a powerful platform to prepare peptide-functionalized PEG hydrogel microarrays. Additionally, we identified a linker composed of 4 glycines to ensure sufficient exposure of the peptide moieties from hydrogel surfaces. Further, we used this system to directly compare cell adhesion abilities of several related RGD peptides: RGD, RGDS, RGDSG and RGDSP. Finally, we combined the peptide-functionalized hydrogel technology with bioinformatics to construct a library composed of 12 different RGD peptides, including 6 unexplored RGD peptides, to develop culture substrates for hiPSC-derived cardiomyocytes (hiPSC-CMs), a cell type known for poor adhesion to synthetic substrates. 2 out of 6 unexplored RGD peptides showed substantial activities to support hiPSC-CMs. Among them, PMQKMRGDVFSP from laminin β4 subunit was found to support the highest adhesion and sarcomere formation of hiPSC-CMs. With bioinformatics, the peptide-functionalized hydrogel microarrays accelerate the discovery of novel biological ligands to develop biomaterials for stem cell and tissue engineering applications.

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Signals from the surface modulate differentiation of human pluripotent stem cells through glycosaminoglycans and integrins

Cited by 58 publications

References 49 publications

Forces of Change: Mechanics Underlying Formation of Functional 3D Organ Buds

Forces of Change: Mechanics Underlying Formation of Functional 3D Organ Buds

Polymer microarray technology for stem cell engineering

Development of peptide-functionalized synthetic hydrogel microarrays for stem cell and tissue engineering applications

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