Nature Medicine11, 228 - 232 (2005)
Published online: 30 January 2005; | doi:10.1038/nm1181
Human embryonic stem cells express an immunogenic nonhuman sialic acid
Maria J Martin1, Alysson Muotri2, Fred Gage2
& Ajit Varki1
1
Glycobiology Research and Training Center and Departments of Medicine and Cellular & Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, Mailcode: 0687, San Diego, California 92093-0687, USA.
2
The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
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.
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
