Long-term human pluripotent stem cell self-renewal on synthetic polymer surfaces

• Published in: Biomaterials 2010-12, Vol.31 (34), p.9135-9144
• Main Authors: Brafman, David A, Chang, Chien W, Fernandez, Antonio, Willert, Karl, Varghese, Shyni, Chien, Shu
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Anhydrides; Cell Lineage - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Defined culture conditions; Dentistry; Differentiation; Embryonic Stem Cells - cytology; Embryonic Stem Cells - drug effects; Embryonic Stem Cells - metabolism; Extracellular matrix; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Gene Expression Regulation - drug effects; Human; Human embryonic stem cells; Human induced pluripotent stem cells; Humans; Integrins - metabolism; Maleic Anhydrides - pharmacology; Matrices; Methyl Ethers - pharmacology; Microarray Analysis; Molecular Weight; Morphology; Pluripotent Stem Cells - cytology; Pluripotent Stem Cells - drug effects; Pluripotent Stem Cells - metabolism; Polymer arrays; Polymers - chemistry; Polymers - pharmacology; Polyvinyls - pharmacology; Regenerative; Stem cells; Surface Properties - drug effects; Surgical implants; Therapy; Time Factors
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2010.08.007

Abstract Realization of the full potential of human pluripotent stem cells (hPSCs) in regenerative medicine requires the development of well-defined culture conditions for their long-term growth and directed differentiation. Current practices for maintaining hPSCs generally utilize empirically determined combinations of feeder cells and other animal-based products, which are expensive, difficult to isolate, subject to batch-to-batch variations, and unsuitable for cell-based therapies. Using a high-throughput screening approach, we identified several polymers that can support self-renewal of hPSCs. While most of these polymers provide support for only a short period of time, we identified a synthetic polymer poly(methyl vinyl ether-alt-maleic anhydride) (PMVE-alt-MA) that supported the long-term attachment, proliferation and self-renewal of HUES1, HUES9, and iPSCs. The hPSCs cultured on PMVE-alt-MA maintained their characteristic morphology, expressed high levels of markers of pluripotency, and retained a normal karyotype. Such cost-effective, polymer-based matrices that support long-term self-renewal and proliferation of hPSCs will not only help to accelerate the translational perspectives of hPSCs, but also provide a platform to elucidate the underlying molecular mechanisms that regulate stem cell proliferation and differentiation.