Clinical and histologic evidence suggest that the liver allograft induces alloimmune hyporesponsiveness in the recipient. Mesenchymal stem cells (MSC) are multipotent non-hematopoietic stromal cells with a potent immunomodulatory role in vivo. Because the immunomodulatory effects of the MSC resemble those seen in liver transplant patients, we hypothesized that liver-derived (L-) MSC play a major role in liver allografts' immunosuppressive capacity on the host.

Methods: L-MSC were generated in vitro from wedge liver biopsy specimens obtained from procured allografts. Bone marrow (BM-) and adipose (A-) MSC were generated from healthy donors. MSC phenotype was assessed with flow cytometry, and their inhibitory effect by mixed leukocyte cultures (HLA-discordant healthy donors or kidney donor-recipient pairs).

Results: L-MSC demonstrated a phenotype very similar to those of BM-MSC and A-MSC: cell surface expression positive for CD44, CD73, CD90, CD105 and HLA-I; and negative for CD14, CD45, and HLA-II. In contrast, the surface expression of PD-L1 was much higher in L-MSC (Fig 1). When introduced to the primary mixed cellular cultures in a ratio of 1:10 (L-MSC:T cells), L-MSC decreased IFNɤ spots by an average of 73% (P<0.001), and alloreactive T cell proliferation by 54.1% (P=0.04). Compared to BM-MSC or A-MSC, the inhibitory effect of L-MSC on T cell responses was significantly superior (e.g. 44% and 63.1% reduction in IFNɤ spots by BM-MSC and A-MSC, respectively, P<0.01). In mixed cultures, L-MSC inhibited proliferation of CD4+ and CD8+ T cell compartments similarly, without affecting the CD4+CD25+Foxp3+ Treg cells.

Conclusions: L-MSC inhibit T cell responses to allostimulation in vitro, and are superior to BM- and A-MSC in this capacity. These results suggest that L-MSC may be a contributor to the liver allograft's regulatory role over the host alloimmune responses.

CITATION INFORMATION: Taner T, Gustafson M, Hansen M, Dietz A, Stegall M. Liver Mesenchymal Stem Cells Inhibit T Cell Alloresponses. Am J Transplant. 2017;17 (suppl 3).

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