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Microfibrous substrate geometry as a critical trigger for organization, self‐renewal, and differentiation of human embryonic stem cells within synthetic 3‐dimensional microenvironments
- Source :
- The FASEB Journal. 26:3240-3251
- Publication Year :
- 2012
- Publisher :
- Wiley, 2012.
-
Abstract
- Substrates used to culture human embryonic stem cells (hESCs) are typically 2-dimensional (2-D) in nature, with limited ability to recapitulate in vivo-like 3-dimensional (3-D) microenvironments. We examined critical determinants of hESC self-renewal in poly-d-lysine-pretreated synthetic polymer-based substrates with variable microgeometries, including planar 2-D films, macroporous 3-D sponges, and microfibrous 3-D fiber mats. Completely synthetic 2-D substrates and 3-D macroporous scaffolds failed to retain hESCs or support self-renewal or differentiation. However, synthetic microfibrous geometries made from electrospun polymer fibers were found to promote cell adhesion, viability, proliferation, self-renewal, and directed differentiation of hESCs in the absence of any exogenous matrix proteins. Mechanistic studies of hESC adhesion within microfibrous scaffolds indicated that enhanced cell confinement in such geometries increased cell-cell contacts and altered colony organization. Moreover, the microfibrous scaffolds also induced hESCs to deposit and organize extracellular matrix proteins like laminin such that the distribution of laminin was more closely associated with the cells than the Matrigel treatment, where the laminin remained associated with the coated fibers. The production of and binding to laminin was critical for formation of viable hESC colonies on synthetic fibrous scaffolds. Thus, synthetic substrates with specific 3-D microgeometries can support hESC colony formation, self-renewal, and directed differentiation to multiple lineages while obviating the stringent needs for complex, exogenous matrices. Similar scaffolds could serve as tools for developmental biology studies in 3-D and for stem cell differentiation in situ and transplantation using defined humanized conditions.—Carlson, A. L., Florek, C. A., Kim, J. J., Neubauer, T., Moore, J. C., Cohen, R. I., Kohn, J., Grumet, M., Moghe, P. V. Microfibrous substrate geometry as a critical trigger for organization, self-renewal, and differentiation of human embryonic stem cells within synthetic 3-dimensional microenvironments.
- Subjects :
- Cellular differentiation
Cell Culture Techniques
Nanotechnology
Biochemistry
Research Communications
Extracellular matrix
Biopolymers
Directed differentiation
Tissue engineering
Cell Adhesion
Genetics
Humans
Polylysine
Cell adhesion
Molecular Biology
Embryonic Stem Cells
Cell Proliferation
Matrigel
Tissue Scaffolds
Chemistry
Cell Differentiation
Stereoisomerism
Embryonic stem cell
Cell biology
Transplantation
Drug Combinations
Tyrosine
Proteoglycans
Collagen
Laminin
Biotechnology
Subjects
Details
- ISSN :
- 15306860 and 08926638
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- The FASEB Journal
- Accession number :
- edsair.doi.dedup.....bb7cc633456b88afd1dd5a1a00b7e666