Xenoantigen-induced immunogenicity in cell culture

by Alexey Bersenev on August 21, 2011 · 1 comment

in cell culture, mesenchymal

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As I noted before, cell therapy developers should forget about use of animal-derived serum in cell culture. We are done with it. I was searching some references, precisely for autologous cells and adult stem cells. Luckily I came across the review by Ian Copland where I found the answer:

Since FBS is xenogenic, human cells exposed to it have the potential to become immunogenic.

There are two studies showed that syngenic lymphocytes and autologous dendritic cells cultured in FBS (and FCS) could cause serious adverse reactions in patients:

 
Spees et al. showed that human mesenchymal stem cells (MSC) could internalize FBS in culture and carry up to 30 mg of xenoantigen:
Internalized antigens must be removed to prepare hypoimmunogenic mesenchymal stem cells for cell and gene therapy. Mol Ther 9(5):747–756

Two groups demonstrated that human bone marrow- and adipose tissue-derived MSC cultured with FBS could express N-glycolylneuraminic acid (Neu5Gc) xenoantigen. Because human serum naturally contains antibody against Neu5Gc, these MSC will trigger immune response and get eliminated:

I’d finish by citation from Ian Copland’s review:

Consequently, transplanted MSCs could release these xenoantigens in vivo to produce a humoral response and potentially present xenoantigens in the context of MHC class I or class II evoking a cellular response. Furthermore, even if these xenoantigens are not initially presented to the exterior, it is possible that during phagocytic processing of apoptotic transplanted somatic cells xenoantigen could enter the MHC class I and MHC class II antigen presentation pathways evoking an indirect increase in immunogenicity to the remaining transplanted cells [135, 149]. As a result, even autologous transplanted MSCs have the potential to be rapidly rejected with the host developing memory cells and natural antibodies which would prevent subsequent use of any cellular therapy where FBS xenoantigens are present.

{ 1 comment… read it below or add one }

Michael An January 16, 2012 at 8:04 pm

Alexey,
I can add two other papers published by scientists at the FDA showing that another bovine antigen apoB is stuck on the cells and cannot be washed off. A strong antibody reaction against apoB is detected in human patients receiving MSCs cultured in FBS medium. Such antibodies will then attack the subsequently administered MSCs and reduce efficacy.
I completely agree with you that FBS should be eliminated from cell therapy.
Michael An

Ref:
1, Bovine apolipoprotein B-100 is a dominant immunogen in therapeutic cell populations cultured in fetal calf serum in mice and humans. http://www.ncbi.nlm.nih.gov/pubmed/17395779

2, Embryonic stem cells cultured in serum-free medium acquire bovine apolipoprotein B-100 from feeder cell layers and serum replacement medium. http://www.ncbi.nlm.nih.gov/pubmed/17951218

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