Combinatorial development of biomaterials for clonal growth of human pluripotent stem cells

Ying Mei; Krishanu Saha; Said R. Bogatyrev; Jing Yang; Andrew L. Hook; Z. Ilke Kalcioglu; Seung Woo Cho; Maisam Mitalipova; Neena Pyzocha; Fredrick Rojas; Krystyn J. Van Vliet; Martyn C. Davies; Morgan R. Alexander; Robert Langer; Rudolf Jaenisch; Daniel G. Anderson

doi:10.1038/nmat2812

Combinatorial development of biomaterials for clonal growth of human pluripotent stem cells

Ying Mei, Krishanu Saha, Said R. Bogatyrev, Jing Yang, Andrew L. Hook, Z. Ilke Kalcioglu, Seung Woo Cho, Maisam Mitalipova, Neena Pyzocha, Fredrick Rojas, Krystyn J. Van Vliet, Martyn C. Davies, Morgan R. Alexander, Robert Langer, Rudolf Jaenisch, Daniel G. Anderson

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461 Citations (Scopus)

Abstract

Both human embryonic stem cells and induced pluripotent stem cells can self-renew indefinitely in culture; however, present methods to clonally grow them are inefficient and poorly defined for genetic manipulation and therapeutic purposes. Here we develop the first chemically defined, xeno-free, feeder-free synthetic substrates to support robust self-renewal of fully dissociated human embryonic stem and induced pluripotent stem cells. Material properties including wettability, surface topography, surface chemistry and indentation elastic modulus of all polymeric substrates were quantified using high-throughput methods to develop structure-function relationships between material properties and biological performance. These analyses show that optimal human embryonic stem cell substrates are generated from monomers with high acrylate content, have a moderate wettability and employ integrin αvβ3 and αvβ5 engagement with adsorbed vitronectin to promote colony formation. The structure-function methodology employed herein provides a general framework for the combinatorial development of synthetic substrates for stem cell culture.

Original language	English
Pages (from-to)	768-778
Number of pages	11
Journal	Nature materials
Volume	9
Issue number	9
DOIs	https://doi.org/10.1038/nmat2812
Publication status	Published - 2010 Sept

Bibliographical note

Funding Information:
We thank all the members of the Langer laboratory and Jaenisch laboratory for helpful discussions and comments on the manuscript. R.J. was supported by NIH grants R37-CA084198, RO1-CA087869 and RO1-HD045022. R.L., R.J. and D.G.A. are advisors to Stemgent and R.L. and R.J. are cofounders of Fate Therapeutics. Financial support for J.Y. and A.H. is from the Wellcome Trust 085246. K.S. is supported by the Society in Science: the Branco Weiss Fellowship. D.G.A., R.L. and Y.M. are supported by NIH DE016516. Z.I.K. was supported by the US Army through the Institute for Soldier Nanotechnologies, under Contract W911NF-07-D-0004 with the US Army Research Office.

All Science Journal Classification (ASJC) codes

Chemistry(all)
Materials Science(all)
Condensed Matter Physics
Mechanics of Materials
Mechanical Engineering

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10.1038/nmat2812

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Mei, Y., Saha, K., Bogatyrev, S. R., Yang, J., Hook, A. L., Kalcioglu, Z. I., Cho, S. W., Mitalipova, M., Pyzocha, N., Rojas, F., Van Vliet, K. J., Davies, M. C., Alexander, M. R., Langer, R., Jaenisch, R., & Anderson, D. G. (2010). Combinatorial development of biomaterials for clonal growth of human pluripotent stem cells. Nature materials, 9(9), 768-778. https://doi.org/10.1038/nmat2812

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title = "Combinatorial development of biomaterials for clonal growth of human pluripotent stem cells",

abstract = "Both human embryonic stem cells and induced pluripotent stem cells can self-renew indefinitely in culture; however, present methods to clonally grow them are inefficient and poorly defined for genetic manipulation and therapeutic purposes. Here we develop the first chemically defined, xeno-free, feeder-free synthetic substrates to support robust self-renewal of fully dissociated human embryonic stem and induced pluripotent stem cells. Material properties including wettability, surface topography, surface chemistry and indentation elastic modulus of all polymeric substrates were quantified using high-throughput methods to develop structure-function relationships between material properties and biological performance. These analyses show that optimal human embryonic stem cell substrates are generated from monomers with high acrylate content, have a moderate wettability and employ integrin αvβ3 and αvβ5 engagement with adsorbed vitronectin to promote colony formation. The structure-function methodology employed herein provides a general framework for the combinatorial development of synthetic substrates for stem cell culture.",

author = "Ying Mei and Krishanu Saha and Bogatyrev, {Said R.} and Jing Yang and Hook, {Andrew L.} and Kalcioglu, {Z. Ilke} and Cho, {Seung Woo} and Maisam Mitalipova and Neena Pyzocha and Fredrick Rojas and {Van Vliet}, {Krystyn J.} and Davies, {Martyn C.} and Alexander, {Morgan R.} and Robert Langer and Rudolf Jaenisch and Anderson, {Daniel G.}",

note = "Funding Information: We thank all the members of the Langer laboratory and Jaenisch laboratory for helpful discussions and comments on the manuscript. R.J. was supported by NIH grants R37-CA084198, RO1-CA087869 and RO1-HD045022. R.L., R.J. and D.G.A. are advisors to Stemgent and R.L. and R.J. are cofounders of Fate Therapeutics. Financial support for J.Y. and A.H. is from the Wellcome Trust 085246. K.S. is supported by the Society in Science: the Branco Weiss Fellowship. D.G.A., R.L. and Y.M. are supported by NIH DE016516. Z.I.K. was supported by the US Army through the Institute for Soldier Nanotechnologies, under Contract W911NF-07-D-0004 with the US Army Research Office.",

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Mei, Y, Saha, K, Bogatyrev, SR, Yang, J, Hook, AL, Kalcioglu, ZI, Cho, SW, Mitalipova, M, Pyzocha, N, Rojas, F, Van Vliet, KJ, Davies, MC, Alexander, MR, Langer, R, Jaenisch, R & Anderson, DG 2010, 'Combinatorial development of biomaterials for clonal growth of human pluripotent stem cells', Nature materials, vol. 9, no. 9, pp. 768-778. https://doi.org/10.1038/nmat2812

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AU - Mei, Ying

AU - Saha, Krishanu

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AU - Hook, Andrew L.

AU - Kalcioglu, Z. Ilke

AU - Cho, Seung Woo

AU - Mitalipova, Maisam

AU - Pyzocha, Neena

AU - Rojas, Fredrick

AU - Van Vliet, Krystyn J.

AU - Davies, Martyn C.

AU - Alexander, Morgan R.

AU - Langer, Robert

AU - Jaenisch, Rudolf

AU - Anderson, Daniel G.

N1 - Funding Information: We thank all the members of the Langer laboratory and Jaenisch laboratory for helpful discussions and comments on the manuscript. R.J. was supported by NIH grants R37-CA084198, RO1-CA087869 and RO1-HD045022. R.L., R.J. and D.G.A. are advisors to Stemgent and R.L. and R.J. are cofounders of Fate Therapeutics. Financial support for J.Y. and A.H. is from the Wellcome Trust 085246. K.S. is supported by the Society in Science: the Branco Weiss Fellowship. D.G.A., R.L. and Y.M. are supported by NIH DE016516. Z.I.K. was supported by the US Army through the Institute for Soldier Nanotechnologies, under Contract W911NF-07-D-0004 with the US Army Research Office.

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Combinatorial development of biomaterials for clonal growth of human pluripotent stem cells

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

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