Human embryonic stem cells express an immunogenic nonhuman sialic acid

Human embryonic stem cells (HESC) can potentially generate every body cell type, making them excellent candidates for cell- and tissue-replacement therapies. HESC are typically cultured with animal-derived 'serum replacements' on mouse feeder layers. Both of these are sources of the nonhum...

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Bibliographic Details
Authors: Martín Martín, María Jesús, Muotri, Alysson, Gage, Fred, Varki, Ajit
Format: article
Status:Draft version
Publication Date:2005
Country:España
Institution:Universidad de Salamanca (USAL)
Repository:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/166957
Online Access:http://hdl.handle.net/10366/166957
Access Level:Embargoed access
Keyword:sialic acids
stem cells
antibodies
Chickens
Green Fluorescent Proteins
Animals
Antibodies
Humans
Cells
Mice
Sialic Acids
Stem Cells
2403 Bioquímica
células
animales
humanos
ratones
ácidos siálicos
proteínas con fluorescencia verde
células madre
pollos
anticuerpos
Description
Summary:Human embryonic stem cells (HESC) can potentially generate every body cell type, making them excellent candidates for cell- and tissue-replacement therapies. HESC are typically cultured with animal-derived 'serum replacements' on mouse feeder layers. Both of these are sources of the nonhuman sialic acid Neu5Gc, against which many humans have circulating antibodies. Both HESC and derived embryoid bodies metabolically incorporate substantial amounts of Neu5Gc under standard conditions. Exposure to human sera with antibodies specific for Neu5Gc resulted in binding of immunoglobulin and deposition of complement, which would lead to cell killing in vivo. Levels of Neu5Gc on HESC and embryoid bodies dropped after culture in heat-inactivated anti-Neu5Gc antibody-negative human serum, reducing binding of antibodies and complement from high-titer sera, while allowing maintenance of the undifferentiated state. Complete elimination of Neu5Gc would be likely to require using human serum with human feeder layers, ideally starting with fresh HESC that have never been exposed to animal products.