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EMBRYONIC STEM CELLS

Embryonic Stem Cells Cultured in Serum-Free Medium Acquire Bovine Apolipoprotein B-100 from Feeder Cell Layers and Serum Replacement Medium

^aDivision of Therapeutic Proteins, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Bethesda, Maryland, USA;
^bDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

Key Words. Apolipoprotein B-100 • Low-density lipoproteins • Fetal calf serum • Conditioned medium • Murine embryonic fibroblasts

Correspondence: Norihisa Sakamoto, M.D., Ph.D., Division of Therapeutic Proteins, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Bethesda, Maryland 20892, USA. Telephone: 301-827-1790; Fax: 301-480-3256; e-mail: norihisha.sakamoto{at}fda.hhs.gov

Received September 5, 2007; accepted for publication October 14, 2007.
First published online in STEM CELLS EXPRESS   October 18, 2007.



Previous studies have demonstrated that cell populations that are cultured with heterologous animal products can acquire xenoantigens, potentially limiting their clinical utility because of immune responses. Embryonic stem cells (ESCs) are an attractive source of multiple potential cellular therapies and are typically derived and routinely cultured on murine embryonic fibroblast (MEF) feeder cell layers in commercially available serum replacement (SR) medium or fetal calf serum (FCS)-containing medium. Recently, we found that a strong antibody response was generated in human subjects after the second infusion of therapeutic cells cultured in FCS-containing medium. This response was specific for bovine apolipoprotein B-100 (apoB-100), which is the major protein component of low-density lipoproteins (LDL) and which targets its binding to abundant low-density lipoprotein receptors on the cell surface, from which it is internalized. Here, we have shown that ESCs cultured on MEFs in SR medium acquired bovine apoB-100 from MEFs and from the SR medium as well. Our findings also suggest that bovine LDL are used as critical nutrients for ESC propagation.

Disclosure of potential conflicts of interest is found at the end of this article.