Three-dimensional porous alginate scaffolds provide a conducive environment for generation of well-vascularized embryoid bodies from human embryonic stem cells

Authors

  • Sharon Gerecht-Nir,

    1. Biotechnology Interdisciplinary Unit, Technion–Israel Institute of Technology, Haifa, Israel
    2. Department of Obstetrics and Gynecology, Rambam Medical Center, POB 9602, Haifa 31096, Israel; telephone: +972-4-854-3236; fax: +972-4-854-2579
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  • Smadar Cohen,

    1. Department of Biotechnology Engineering and the Institute for Applied Biosciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
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  • Anna Ziskind,

    1. Department of Obstetrics and Gynecology, Rambam Medical Center, POB 9602, Haifa 31096, Israel; telephone: +972-4-854-3236; fax: +972-4-854-2579
    2. Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel
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  • Joseph Itskovitz-Eldor

    Corresponding author
    1. Department of Obstetrics and Gynecology, Rambam Medical Center, POB 9602, Haifa 31096, Israel; telephone: +972-4-854-3236; fax: +972-4-854-2579
    2. Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel
    • Department of Obstetrics and Gynecology, Rambam Medical Center, POB 9602, Haifa 31096, Israel; telephone: +972-4-854-3236; fax: +972-4-854-2579
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Abstract

Differentiation of human embryonic stem cells (hESCs) can be instigated through the formation of embryo-like aggregates in suspension, termed human embryoid bodies (hEBs). Controlling cell aggregation and agglomeration during hEBs formation has a profound effect on the extent of cell proliferation and differentiation. In a previous work, we showed that control over hEBs formation and differentiation can be achieved via cultivation of hESC suspensions in a rotating bioreactor system. We now report that hEBs can be generated directly from hESC suspensions within three-dimensional (3D) porous alginate scaffolds. The confining environments of the alginate scaffold pores enabled efficient formation of hEBs with a relatively high degree of cell proliferation and differentiation; encouraged round, small-sized hEBs; and induced vasculogenesis in the forming hEBs to a greater extent than in static or rotating cultures. We therefore conclude that differentiation of hEBs can be induced and directed by physical constraints in addition to chemical cues. © 2004 Wiley Periodicals, Inc.

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