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 Blood, 1 January 2008, Vol. 111, No. 1, pp. 430-438.
Prepublished online as a Blood First Edition Paper on October 1, 2007; DOI 10.1182/blood-2007-03-078774.

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TRANSPLANTATION

Immunogenicity of umbilical cord tissue–derived cells

Patricia S. Cho1, Darin J. Messina2, Erica L. Hirsh1, Nina Chi2, Stephanie N. Goldman2, Diana P. Lo1, Ian R. Harris2, Sicco H. Popma2, David H. Sachs1, and Christene A. Huang1

1 Transplantation Biology Research Center, Massachusetts General Hospital, Boston; and 2 Centocor R&D, Stem Cell Internal Venture, Radnor, PA

Umbilical cord tissue provides a unique source of cells with potential for tissue repair. Umbilical cord tissue–derived cells (UTCs) are MHC class I (MHCI) dull and negative for MHC class II (MHCII), but can be activated to increase MHCI and to express MHCII with IFN-{gamma} stimulation. Mesenchymal stem cells with similar characteristics have been inferred to be nonimmunogenic; however, in most cases, immunogenicity was not directly assessed. Using UTC from Massachusetts General Hospital MHC-defined miniature swine, we assessed immunogenicity across a full MHC barrier. Immunogenicity was assessed by in vitro assays including mixed lymphocyte reaction (MLR) and flow cytometry to detect serum alloantibody. A single injection of MHC-mismatched unactivated UTCs did not induce a detectable immune response. When injected in an inflamed region, injected repeatedly in the same region or stimulated with IFN-{gamma} prior to injection, UTCs were immunogenic. As clinical cellular repair strategies may involve injection of allogeneic cells into inflamed regions of damaged tissue or repeated doses of cells to achieve the desired benefit, our results on the immunogenicity of these cells in these circumstances may have important implications for optimal success and functional improvement for this cellular treatment strategy for diseased tissues.


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