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Crosslinking of extracellular matrix scaffolds derived from pluripotent stem cell aggregates modulates neural differentiation

Paper ID Volume ID Publish Year Pages File Format Full-Text
188 12 2016 11 PDF Available
Title
Crosslinking of extracellular matrix scaffolds derived from pluripotent stem cell aggregates modulates neural differentiation
Abstract

At various developmental stages, pluripotent stem cells (PSCs) and their progeny secrete a large amount of extracellular matrices (ECMs) which could interact with regulatory growth factors to modulate stem cell lineage commitment. ECMs derived from PSC can be used as unique scaffolds that provide broad signaling capacities to mediate cellular differentiation. However, the rapid degradation of ECMs can impact their applications as the scaffolds for in vitro cell expansion and in vivo transplantation. To address this issue, this study investigated the effects of crosslinking on the ECMs derived from embryonic stem cells (ESCs) and the regulatory capacity of the crosslinked ECMs on the proliferation and differentiation of reseeded ESC-derived neural progenitor cells (NPCs). To create different biological cues, undifferentiated aggregates, spontaneous embryoid bodies, and ESC-derived NPC aggregates were decellularized. The derived ECMs were crosslinked using genipin or glutaraldehyde to enhance the scaffold stability. ESC-derived NPC aggregates were reseeded on different ECM scaffolds and differential cellular compositions of neural progenitors, neurons, and glial cells were observed. The results indicate that ESC-derived ECM scaffolds affect neural differentiation through intrinsic biological cues and biophysical properties. These scaffolds have potential for in vitro cell culture and in vivo tissue regeneration study.Statement of significanceDynamic interactions of acellular extracellular matrices and stem cells are critical for lineage-specific commitment and tissue regeneration. Understanding the synergistic effects of biochemical, biological, and biophysical properties of acellular matrices would facilitate scaffold design and the functional regulation of stem cells.The present study assessed the influence of crosslinked embryonic stem cell-derived extracellular matrix on neural differentiation and revealed the synergistic interactions of various matrix properties.While embryonic stem cell-derived matrices have been assessed as tissue engineering scaffolds, the impact of crosslinking on the embryonic stem cell-derived matrices to modulate neural differentiation has not been studied.The results from this study provide novel knowledge on the interface of embryonic stem cell-derived extracellular matrix and neural aggregates. The findings reported in this manuscript are significant for stem cell differentiation toward the applications in stem cell-based drug screening, disease modeling, and cell therapies.

Graphical abstractSchematic diagram of the experiments. Embryonic stem cells (ESCs) were seeded in suspension to generate undifferentiated aggregates (AGG), spontaneous embryoid bodies (EBs), or to derive neural progenitor cell (NPC) aggregates. The three types of aggregates were then decellularized (DE) to generate DE-A, DE-E, and DE-N scaffolds. The derived extracellular matrices (ECMs) were treated with genipin (G) or glutaraldehyde (GL) to obtain the crosslinked scaffolds. The non-crosslinked ECMs were used as controls (C). ESC-derived NPCs were seeded onto various ECM scaffolds and characterized.Figure optionsDownload full-size imageDownload high-quality image (178 K)Download as PowerPoint slide

Keywords
Pluripotent stem cells; Extracellular matrix; Crosslinking; Neural progenitor cells; Decellularization
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Crosslinking of extracellular matrix scaffolds derived from pluripotent stem cell aggregates modulates neural differentiation
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Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 30, 15 January 2016, Pages 222–232
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us