The effect of matrix composition of 3D constructs on embryonic stem cell differentiation

Battista, Sabrina; Guarnieri, Daniela; Borselli, Cristina; Zeppetelli, S.; Borzacchiello, Assunta; Mayol, Laura; Gerbasio, Diego; Keene, Douglas R.; Ambrosio, Luigi; Netti, Paolo A.

doi:10.1016/j.biomaterials.2005.04.003

Cited by 225 publications

(165 citation statements)

References 24 publications

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“…22,[31][32][33][34][35] Furthermore, differentiation toward a target tissue is improved if the ECM protein architecture closely resembles the in vivo ECM of the targeted tissue. 31,35,36 In addition, three-dimensional cultures have been shown to improve differentiation of ES cells through increased cell-cell and matrix association. 37 Therefore, it was reasoned that an assessment of ES cell response to our acellular kidney model, especially given the complex heterogeneous histoarchitecture, is an important step in future tissue engineering endeavors.…”

Section: Discussionmentioning

confidence: 99%

Embryonic Stem Cells Proliferate and Differentiate when Seeded into Kidney Scaffolds

Ross

Williams²,

Hamazaki³

et al. 2009

Journal of the American Society of Nephrology

370

266

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The scarcity of transplant allografts for diseased organs has prompted efforts at tissue regeneration using seeded scaffolds, an approach hampered by the enormity of cell types and complex architectures. Our goal was to decellularize intact organs in a manner that retained the matrix signal for differentiating pluripotent cells. We decellularized intact rat kidneys in a manner that preserved the intricate architecture and seeded them with pluripotent murine embryonic stem cells antegrade through the artery or retrograde through the ureter. Primitive precursor cells populated and proliferated within the glomerular, vascular, and tubular structures. Cells lost their embryonic appearance and expressed immunohistochemical markers for differentiation. Cells not in contact with the basement membrane matrix became apoptotic, thereby forming lumens. These observations suggest that the extracellular matrix can direct regeneration of the kidney, and studies using seeded scaffolds may help define differentiation pathways.

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Section: Discussionmentioning

confidence: 99%

Embryonic Stem Cells Proliferate and Differentiate when Seeded into Kidney Scaffolds

Ross

Williams²,

Hamazaki³

et al. 2009

Journal of the American Society of Nephrology

370

266

View full text Add to dashboard Cite

show abstract

“…Instead we have proposed that an appropriately prepared matrix 13,14 will retain the signals to trigger site-specific differentiation of pluripotent precursor cells, and thereby launch a cascade of matrix-cell, cell-cell 15 and cell-matrix events culminating in cycles of organ differentiation and remodeling of the original scaffold. The concept of matrix-induced cellular differentiation is not new, [16][17][18][19][20][21] and extends back to pioneering work by MJ Bissell. 22 In addition, and integral to our hypothesis, is that the ontogeny of the differentiation of the seeded precursor cells will be embryologically correct, as would be the subsequent changes to matrix and basement membranes they produce.…”

Section: Discussionmentioning

confidence: 99%

Mouse stem cells seeded into decellularized rat kidney scaffolds endothelialize and remodel basement membranes

et al. 2012

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Conclusion: We provide new evidence for matrix-to-cell signaling in acellular whole organ scaffolds that induces differentiation of pluripotent precursor cells to endothelial lineage. Production of mouse basement membrane supports remodeling of host (rat)-derived scaffolds and thereby warrants further investigation as a promising approach for xenotransplantation.Methods: We previously showed that murine embryonic stem cells arterially seeded into acellular rat whole kidney scaffolds multiply and demonstrate morphologic, immunohistochemical and gene expression evidence for differentiation. Vascular cell endothelialization was now further tested by endothelial specific BsLB4 lectin and anti-VEGFR2 (Flk1) antibodies. Remodeling of the matrix basement membranes from rat to mouse ("murinization") was assessed by a monoclonal antibody specific for mouse laminin b1 chain.

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“…Importantly, bioengineering-based approaches applied to EBs have proven very useful in addressing the role of microenvironmental parameters that are difficult to study with traditional culture approaches (Bratt-Leal et al, 2009;Woodford and Zandstra, 2012). For example, such platforms have been instrumental in demonstrating that aggregate size and shape control stem cell fate within EBs (Bauwens et al, 2008;Hwang et al, 2009;Karp et al, 2007) and implicating the ECM as a potent modulator of EB differentiation (Battista et al, 2005;Li et al, 2013). The recently introduced stem cell-derived organoids have demonstrated that, aside from modeling early embryogenesis, stem cells can be used to mimic aspects of rodent and human organogenesis.…”

Section: Self-organizing Stem Cellsmentioning

confidence: 99%

Bioengineering approaches to guide stem cell-based organogenesis

2014

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During organogenesis, various molecular and physical signals are orchestrated in space and time to sculpt multiple cell types into functional tissues and organs. The complex and dynamic nature of the process has hindered studies aimed at delineating morphogenetic mechanisms in vivo, particularly in mammals. Recent demonstrations of stem cell-driven tissue assembly in culture offer a powerful new tool for modeling and dissecting organogenesis. However, despite the highly organotypic nature of stem cell-derived tissues, substantial differences set them apart from their in vivo counterparts, probably owing to the altered microenvironment in which they reside and the lack of mesenchymal influences. Advances in the biomaterials and microtechnology fields have, for example, afforded a high degree of spatiotemporal control over the cellular microenvironment, making it possible to interrogate the effects of individual microenvironmental components in a modular fashion and rapidly identify organ-specific synthetic culture models. Hence, bioengineering approaches promise to bridge the gap between stem cell-driven tissue formation in culture and morphogenesis in vivo, offering mechanistic insight into organogenesis and unveiling powerful new models for drug discovery, as well as strategies for tissue regeneration in the clinic. We draw on several examples of stem cellderived organoids to illustrate how bioengineering can contribute to tissue formation ex vivo. We also discuss the challenges that lie ahead and potential ways to overcome them.

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The effect of matrix composition of 3D constructs on embryonic stem cell differentiation

Cited by 225 publications

References 24 publications

Embryonic Stem Cells Proliferate and Differentiate when Seeded into Kidney Scaffolds

Embryonic Stem Cells Proliferate and Differentiate when Seeded into Kidney Scaffolds

Mouse stem cells seeded into decellularized rat kidney scaffolds endothelialize and remodel basement membranes

Bioengineering approaches to guide stem cell-based organogenesis

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