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First published online January 12, 2006
Stem Cells Vol. 24 No. 5 May 2006, pp. 1246 -1253
doi:10.1634/stemcells.2005-0235; www.StemCells.com
© 2006 AlphaMed Press

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TISSUE-SPECIFIC STEM CELLS

The Immunogenicity of Human Adipose-Derived Cells: Temporal Changes In Vitro

Kevin McIntosha, Sanjin Zvonicb, Sara Garretta, James B. Mitchella, Z. Elizabeth Floydb, Lora Hammilla, Amy Klosterc, Yuan Di Halvorsenc,d, Jenny P. Tinge, Robert W. Stormsf, Brian Gohb, Gail Kilroyb, Xiying Wua, Jeffrey M. Gimbleb,c,f

a Cognate Therapeutics, Inc., Baltimore, Maryland, USA;
b Stem Cell Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA;
c Artecel Sciences, Durham, North Carolina, USA;
d CuraGen Corporation, Branford, Connecticut, USA;
e Lineberger Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA;
f Duke University Medical Center, Durham, North Carolina, USA

Key Words. Human • Mixed lymphocyte reaction • Immunosuppressive • Immunogenic • Multipotent • Tissue engineering • Regenerative medicine • Adipose-derived stem cells

Correspondence: Jeffrey M. Gimble, M.D., Ph.D., Stem Cell Laboratory, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, Louisiana 70808, USA. Telephone: 225-763-3171; Fax: 225-763-0273; e-mail: gimblejm{at}pbrc.edu

Received May 24, 2005; accepted for publication December 28, 2005.
Regenerative medical techniques will require an abundant source of human adult stem cells that can be readily available at the point of care. The ability to use unmatched allogeneic stem cells will help achieve this goal. Since adipose tissue represents an untapped reservoir of human cells, we have compared the immunogenic properties of freshly isolated, collagenase-digested human adipose tissue-derived stromal vascular fraction cells (SVFs) relative to passaged, plastic-adherent adipose-derived stem cells (ASCs). Parallel studies have shown that adherence to plastic and subsequent expansion of human adipose-derived cells selects for a relatively homogeneous cell population based on immunophenotype. Consistent with these findings, the presence of hematopoietic-associated markers (CD11a, CD14, CD45, CD86, and histocompatible locus antigen-DR [HLA-DR]) detected on the heterogeneous SVF cell population decreased upon subsequent passage of the ASCs. In mixed lymphocyte reactions (MLRs), SVFs, and early passage ASCs stimulated proliferation by allogeneic responder T cells. In contrast, the ASCs beyond passage P1 failed to elicit a response from T cells. Indeed, late passage ASCs actually suppressed the MLR response. Although these results support the feasibility of allogeneic human ASC transplantation, confirmatory in vivo animal studies will be required.




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